TY  - JOUR
AU  - Ludwig, Gerd
AU  - Ranđelović, Ivan
AU  - Dimić, Dušan
AU  - Komazec, Teodora
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Rüffer, Tobias
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6642
AB  - The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the “piano stool” type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.
PB  - Basel: MDPI
T2  - Biomolecules
T1  - (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand
IS  - 4
VL  - 14
DO  - 10.3390/biom14040420
SP  - 420
ER  - 

@article{
author = "Ludwig, Gerd and Ranđelović, Ivan and Dimić, Dušan and Komazec, Teodora and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Rüffer, Tobias and Kaluđerović, Goran N.",
year = "2024",
abstract = "The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the “piano stool” type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.",
publisher = "Basel: MDPI",
journal = "Biomolecules",
title = "(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand",
number = "4",
volume = "14",
doi = "10.3390/biom14040420",
pages = "420"
}

Ludwig, G., Ranđelović, I., Dimić, D., Komazec, T., Maksimović-Ivanić, D., Mijatović, S., Rüffer, T.,& Kaluđerović, G. N.. (2024). (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand. in Biomolecules
Basel: MDPI., 14(4), 420.
https://doi.org/10.3390/biom14040420

Ludwig G, Ranđelović I, Dimić D, Komazec T, Maksimović-Ivanić D, Mijatović S, Rüffer T, Kaluđerović GN. (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand. in Biomolecules. 2024;14(4):420.
doi:10.3390/biom14040420 .

Ludwig, Gerd, Ranđelović, Ivan, Dimić, Dušan, Komazec, Teodora, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Rüffer, Tobias, Kaluđerović, Goran N., "(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand" in Biomolecules, 14, no. 4 (2024):420,
https://doi.org/10.3390/biom14040420 . .

TY  - JOUR
AU  - Kasalović, Marijana P.
AU  - Dimić, Dušan
AU  - Jelača, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Zmejkovski, Bojana B.
AU  - Schreiner, Simon H. F.
AU  - Rüffer, Tobias
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6626
AB  - A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells
IS  - 3
VL  - 17
DO  - 10.3390/ph17030372
SP  - 372
ER  - 

@article{
author = "Kasalović, Marijana P. and Dimić, Dušan and Jelača, Sanja and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Zmejkovski, Bojana B. and Schreiner, Simon H. F. and Rüffer, Tobias and Pantelić, Nebojša Đ. and Kaluđerović, Goran N.",
year = "2024",
abstract = "A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells",
number = "3",
volume = "17",
doi = "10.3390/ph17030372",
pages = "372"
}

Kasalović, M. P., Dimić, D., Jelača, S., Maksimović-Ivanić, D., Mijatović, S., Zmejkovski, B. B., Schreiner, S. H. F., Rüffer, T., Pantelić, N. Đ.,& Kaluđerović, G. N.. (2024). Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells. in Pharmaceuticals
Basel: MDPI., 17(3), 372.
https://doi.org/10.3390/ph17030372

Kasalović MP, Dimić D, Jelača S, Maksimović-Ivanić D, Mijatović S, Zmejkovski BB, Schreiner SHF, Rüffer T, Pantelić NĐ, Kaluđerović GN. Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells. in Pharmaceuticals. 2024;17(3):372.
doi:10.3390/ph17030372 .

Kasalović, Marijana P., Dimić, Dušan, Jelača, Sanja, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Zmejkovski, Bojana B., Schreiner, Simon H. F., Rüffer, Tobias, Pantelić, Nebojša Đ., Kaluđerović, Goran N., "Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells" in Pharmaceuticals, 17, no. 3 (2024):372,
https://doi.org/10.3390/ph17030372 . .

TY  - JOUR
AU  - Bovan, Dijana
AU  - Krajnović, Tamara
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6576
AB  - Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.
PB  - Springer Nature
T2  - Molecular Biology Reports
T1  - Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro
IS  - 1
VL  - 51
DO  - 10.1007/s11033-023-09093-x
SP  - 218
ER  - 

@article{
author = "Bovan, Dijana and Krajnović, Tamara and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.",
publisher = "Springer Nature",
journal = "Molecular Biology Reports",
title = "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro",
number = "1",
volume = "51",
doi = "10.1007/s11033-023-09093-x",
pages = "218"
}

Bovan, D., Krajnović, T., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2024). Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports
Springer Nature., 51(1), 218.
https://doi.org/10.1007/s11033-023-09093-x

Bovan D, Krajnović T, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports. 2024;51(1):218.
doi:10.1007/s11033-023-09093-x .

Bovan, Dijana, Krajnović, Tamara, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro" in Molecular Biology Reports, 51, no. 1 (2024):218,
https://doi.org/10.1007/s11033-023-09093-x . .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Jovanović, Ivan
AU  - Bovan, Dijana
AU  - Jovanović, Marina Z.
AU  - Jurišević, Milena M.
AU  - Dunđerović, Duško
AU  - Dajić-Stevanović, Zora
AU  - Arsenijević, Nebojša
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6575
AB  - Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response
IS  - 3
VL  - 17
DO  - 10.3390/ph17030286
SP  - 286
ER  - 

@article{
author = "Jelača, Sanja and Jovanović, Ivan and Bovan, Dijana and Jovanović, Marina Z. and Jurišević, Milena M. and Dunđerović, Duško and Dajić-Stevanović, Zora and Arsenijević, Nebojša and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response",
number = "3",
volume = "17",
doi = "10.3390/ph17030286",
pages = "286"
}

Jelača, S., Jovanović, I., Bovan, D., Jovanović, M. Z., Jurišević, M. M., Dunđerović, D., Dajić-Stevanović, Z., Arsenijević, N., Mijatović, S.,& Maksimović-Ivanić, D.. (2024). Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals
Basel: MDPI., 17(3), 286.
https://doi.org/10.3390/ph17030286

Jelača S, Jovanović I, Bovan D, Jovanović MZ, Jurišević MM, Dunđerović D, Dajić-Stevanović Z, Arsenijević N, Mijatović S, Maksimović-Ivanić D. Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals. 2024;17(3):286.
doi:10.3390/ph17030286 .

Jelača, Sanja, Jovanović, Ivan, Bovan, Dijana, Jovanović, Marina Z., Jurišević, Milena M., Dunđerović, Duško, Dajić-Stevanović, Zora, Arsenijević, Nebojša, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response" in Pharmaceuticals, 17, no. 3 (2024):286,
https://doi.org/10.3390/ph17030286 . .

TY  - JOUR
AU  - Kasalović, Marijana P.
AU  - Jelača, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Lađarević, Jelena
AU  - Radovanović, Lidija
AU  - Božić, Bojan
AU  - Mijatović, Sanja
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6268
AB  - Three new diphenyltin(IV) complexes, bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato)diphenyltin(IV) (1), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (2), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (3), were synthesized and characterized by elemental microanalysis, FT-IR spectroscopy, and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. Crystal structure of ligand precursor, 3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoic acid (HL1), has been determined by X-ray diffraction studies. Asymmetric bidentate coordination of the carboxylato ligands and skew trapezoidal structures are assumed for the synthesized complexes. In vitro anticancer activity of the synthesized diphenyltin(IV) complexes was evaluated against three human: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three mouse tumor cell lines: 4 T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the range from 0.1 to 3.7 μM. Flow cytometric analysis and fluorescent microscopy suggest that complex 1 induces caspase-dependent apoptosis followed with strong blockade of cell division in HCT116 cells. Since complex 1 showed ROS/RNS scavenging potential mentioned cytotoxicity was not connected with oxidative stress.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies
VL  - 250
DO  - 10.1016/j.jinorgbio.2023.112399
SP  - 112399
ER  - 

@article{
author = "Kasalović, Marijana P. and Jelača, Sanja and Maksimović-Ivanić, Danijela and Lađarević, Jelena and Radovanović, Lidija and Božić, Bojan and Mijatović, Sanja and Pantelić, Nebojša Đ. and Kaluđerović, Goran N.",
year = "2024",
abstract = "Three new diphenyltin(IV) complexes, bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato)diphenyltin(IV) (1), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (2), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (3), were synthesized and characterized by elemental microanalysis, FT-IR spectroscopy, and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. Crystal structure of ligand precursor, 3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoic acid (HL1), has been determined by X-ray diffraction studies. Asymmetric bidentate coordination of the carboxylato ligands and skew trapezoidal structures are assumed for the synthesized complexes. In vitro anticancer activity of the synthesized diphenyltin(IV) complexes was evaluated against three human: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three mouse tumor cell lines: 4 T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the range from 0.1 to 3.7 μM. Flow cytometric analysis and fluorescent microscopy suggest that complex 1 induces caspase-dependent apoptosis followed with strong blockade of cell division in HCT116 cells. Since complex 1 showed ROS/RNS scavenging potential mentioned cytotoxicity was not connected with oxidative stress.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies",
volume = "250",
doi = "10.1016/j.jinorgbio.2023.112399",
pages = "112399"
}

Kasalović, M. P., Jelača, S., Maksimović-Ivanić, D., Lađarević, J., Radovanović, L., Božić, B., Mijatović, S., Pantelić, N. Đ.,& Kaluđerović, G. N.. (2024). Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies. in Journal of Inorganic Biochemistry
Elsevier., 250, 112399.
https://doi.org/10.1016/j.jinorgbio.2023.112399

Kasalović MP, Jelača S, Maksimović-Ivanić D, Lađarević J, Radovanović L, Božić B, Mijatović S, Pantelić NĐ, Kaluđerović GN. Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies. in Journal of Inorganic Biochemistry. 2024;250:112399.
doi:10.1016/j.jinorgbio.2023.112399 .

Kasalović, Marijana P., Jelača, Sanja, Maksimović-Ivanić, Danijela, Lađarević, Jelena, Radovanović, Lidija, Božić, Bojan, Mijatović, Sanja, Pantelić, Nebojša Đ., Kaluđerović, Goran N., "Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies" in Journal of Inorganic Biochemistry, 250 (2024):112399,
https://doi.org/10.1016/j.jinorgbio.2023.112399 . .

TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Stockmann, Philipp
AU  - Mijatović, Sanja
AU  - Kuhnert, Lydia
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6489
AB  - Abstract: The ABCG2 transporter protein, as part of several known mechanisms involved in multidrug
resistance, has the ability to transport a broad spectrum of substrates out of the cell and is,
therefore, considered as a potential target to improve cancer therapies or as an approach to combat
drug resistance in cancer. We have previously reported carborane-functionalized quinazoline derivatives
as potent inhibitors of human ABCG2 which effectively reversed breast cancer resistance protein
(BCRP)-mediated mitoxantrone resistance. In this work, we present the evaluation of our most
promising carboranyl BCRP inhibitors regarding their toxicity towards ABCG2-expressing cancer cell
lines (MCF-7, doxorubicin-resistant MCF-7 or MCF-7 Doxo, HT29, and SW480) and, consequently,
with the co-administration of an inhibitor and therapeutic agent, their ability to increase the efficacy
of therapeutics with the successful inhibition of ABCG2. The results obtained revealed synergistic
effects of several inhibitors in combination with doxorubicin or cisplatin. Compounds DMQCa,
DMQCc, and DMQCd showed a decrease in IC50 value in ABCB1- and ABCG2-expressing SW480
cells, suggesting a possible targeting of both transporters. In an HT29 cell line, with the highest
expression of ABCG2 among the tested cell lines, using co-treatment of doxorubicin and DMQCd, the
effective inhibitory concentration of the antineoplastic agent could be reduced by half. Interestingly,
co-treatment of compound QCe with cisplatin, which is not an ABCG2 substrate, showed synergistic
effects in MCF-7 Doxo and HT29 cells (IC50 values halved or reduced by 20%, respectively). However,
a literature-known upregulation of cisplatin-effluxing ABC transporters and their effective inhibition
by the carborane derivatives emerges as a possible reason.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin
IS  - 11
VL  - 16
DO  - 10.3390/ph16111582
SP  - 1582
ER  - 

@article{
author = "Paskaš, Svetlana and Stockmann, Philipp and Mijatović, Sanja and Kuhnert, Lydia and Honscha, Walther and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Abstract: The ABCG2 transporter protein, as part of several known mechanisms involved in multidrug
resistance, has the ability to transport a broad spectrum of substrates out of the cell and is,
therefore, considered as a potential target to improve cancer therapies or as an approach to combat
drug resistance in cancer. We have previously reported carborane-functionalized quinazoline derivatives
as potent inhibitors of human ABCG2 which effectively reversed breast cancer resistance protein
(BCRP)-mediated mitoxantrone resistance. In this work, we present the evaluation of our most
promising carboranyl BCRP inhibitors regarding their toxicity towards ABCG2-expressing cancer cell
lines (MCF-7, doxorubicin-resistant MCF-7 or MCF-7 Doxo, HT29, and SW480) and, consequently,
with the co-administration of an inhibitor and therapeutic agent, their ability to increase the efficacy
of therapeutics with the successful inhibition of ABCG2. The results obtained revealed synergistic
effects of several inhibitors in combination with doxorubicin or cisplatin. Compounds DMQCa,
DMQCc, and DMQCd showed a decrease in IC50 value in ABCB1- and ABCG2-expressing SW480
cells, suggesting a possible targeting of both transporters. In an HT29 cell line, with the highest
expression of ABCG2 among the tested cell lines, using co-treatment of doxorubicin and DMQCd, the
effective inhibitory concentration of the antineoplastic agent could be reduced by half. Interestingly,
co-treatment of compound QCe with cisplatin, which is not an ABCG2 substrate, showed synergistic
effects in MCF-7 Doxo and HT29 cells (IC50 values halved or reduced by 20%, respectively). However,
a literature-known upregulation of cisplatin-effluxing ABC transporters and their effective inhibition
by the carborane derivatives emerges as a possible reason.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin",
number = "11",
volume = "16",
doi = "10.3390/ph16111582",
pages = "1582"
}

Paskaš, S., Stockmann, P., Mijatović, S., Kuhnert, L., Honscha, W., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin. in Pharmaceuticals
Basel: MDPI., 16(11), 1582.
https://doi.org/10.3390/ph16111582

Paskaš S, Stockmann P, Mijatović S, Kuhnert L, Honscha W, Hey-Hawkins E, Maksimović-Ivanić D. Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin. in Pharmaceuticals. 2023;16(11):1582.
doi:10.3390/ph16111582 .

Paskaš, Svetlana, Stockmann, Philipp, Mijatović, Sanja, Kuhnert, Lydia, Honscha, Walther, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Carborane-Based ABCG2-Inhibitors Sensitize ABC-(Over)Expressing Cancer Cell Lines for Doxorubicin and Cisplatin" in Pharmaceuticals, 16, no. 11 (2023):1582,
https://doi.org/10.3390/ph16111582 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Krajnović, Tamara
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6436
AB  - Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
DO  - 10.1002/cmdc.202300506
SP  - e202300506
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Krajnović, Tamara and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres",
doi = "10.1002/cmdc.202300506",
pages = "e202300506"
}

Stockmann, P., Kuhnert, L., Krajnović, T., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem
Wiley-VCH GmbH., e202300506.
https://doi.org/10.1002/cmdc.202300506

Stockmann P, Kuhnert L, Krajnović T, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem. 2023;:e202300506.
doi:10.1002/cmdc.202300506 .

Stockmann, Philipp, Kuhnert, Lydia, Krajnović, Tamara, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres" in ChemMedChem (2023):e202300506,
https://doi.org/10.1002/cmdc.202300506 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Krajnović, Tamara
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6425
AB  - Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
DO  - 10.1002/cmdc.202300506
SP  - e202300506
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Krajnović, Tamara and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP-binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP-mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron-carbon cluster, namely closodicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2-phenylquinazolin-4-amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2-overexpressing cancers.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres",
doi = "10.1002/cmdc.202300506",
pages = "e202300506"
}

Stockmann, P., Kuhnert, L., Krajnović, T., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem
Wiley-VCH GmbH., e202300506.
https://doi.org/10.1002/cmdc.202300506

Stockmann P, Kuhnert L, Krajnović T, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres. in ChemMedChem. 2023;:e202300506.
doi:10.1002/cmdc.202300506 .

Stockmann, Philipp, Kuhnert, Lydia, Krajnović, Tamara, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2-Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres" in ChemMedChem (2023):e202300506,
https://doi.org/10.1002/cmdc.202300506 . .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6262
AB  - Меланом се сматра најагресивнијим типом канцера коже. Услед иницијалне
или стечене резистенције и бројних нежељених дејстава, постојећи терапеутски
режими за метастатски меланом нису довољно ефикасни. Стога, меланом остаје
удружен са високом стопом смртности. Упркос опсежним терапеутским протоколима, стопа излечења инвазивних облика тумора је поражавајуће ниска те се
поставља питање шта је погрешно у актуленом приступу у онкотерапији. Главни критеријум за одабир нових антитуморских лекова превасходно је базиран
на њиховој способности да индукују апоптозу. Међутим, све више литературних
података доводе у везу агресивне терапеутске приступе који се базирају на индукцији апоптозе у туморима високог градуса, које карактерише присуство ћелија
слабо диферентованог фенотипа, са туморском прогресијом до које долази услед
компензаторне пролиферације. Решење проблема почива у повећању нивоа диференцијације тумора чиме ће опадати пролиферација индукована апоптозом.
Диферeнцијациона терапија представља нови концепт у терапији агресивних малигнитета. Многи диференцијациони агенси су природног порекла. У циљу повећања ефикасности и смањења токсичности конвенционалних терапија, стандардни терапеутски протоколи се често комбинују са комплементарном медицином,
где водећу позицију заузимају природни производи изоловани из биљака. Једну
од највећих и најразноврснијих класа секундарних биљних метаболита која се
одликује израженим антиканцерским потенцијалом представљају флавоноиди.
Пренилфлавоноиди из хмељa имају велики потенцијал да изазову промену малигног фенотипа у мирнији, функционално дефинисанији облик, ближи здравом
пандану истог или различитог ткива. Овакав приступ недовољно је истражен
чиме се отварају многе могућности како у научном тако и у комерцијалном смислу. Фокус овог предавања је стављен на пренилфлавоноид - изоксантохумол у
контексту евентуалне терапије меланома и креирања протокола који би подигли
ефикасност постојећих третмана комерцијалним хемотерапеутицима.
AB  - Melanoma is considered the most aggressive type of skin cancer. Due to initial or
acquired resistance and numerous side effects, existing therapeutic regimens for metastatic
melanoma are not sufficiently effective. Therefore, melanoma remains associated with a
high mortality rate. Despite extensive therapeutic protocols, the curation rate for invasive
forms of tumors is quite low, and the question arises as to what is wrong with the current
approach in oncotherapy. The main criterion for the selection of new antitumor drugs is
primarily based on their ability to induce apoptosis. However, numerous literature data
link aggressive therapeutic approaches based on the induction of apoptosis in high grade
tumors, which are characterized by the presence of cells with a low-differentiated
phenotype, with tumor progression that occurs due to compensatory proliferation. The
solution to the problem lies in increasing the level of tumor differentiation, which will
decrease proliferation induced by apoptosis. Differentiation therapy represents a new
concept in the therapy of aggressive malignancies. Many differentiation agents are of
natural origin. In order to increase the efficacy and reduce the toxicity of conventional
therapies, standard therapeutic protocols are often combined with complementary
medicine, where the leading position is occupied by natural products isolated from
plants. Flavonoids are one of the largest and most diverse classes of secondary plant
metabolites, well-known for their pronounced anticancer potential. Prenylflavonoids
from the hop plant have a great potential to trigger a change of the malignant phenotype
into a quiescent, more functionally defined form, closer to the healthy counterpart of the
same or different tissue. This approach has mainly been unexplored, opening up many
possibilities in both scientific and commercial terms. The focus of this lecture will be
on prenylflavonoid - isoxanthohumol in the context of possible melanoma therapy and
the creation of protocols that would increase the effectiveness of existing conventional
chemotherapy.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Нутрацеутици хмеља у сусрет терапији метастатског меланома
T1  - Nutraceuticals from hops in the treatment of metastatic melanoma
SP  - 81
EP  - 84
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6262
ER  - 

@conference{
author = "Krajnović, Tamara and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2023",
abstract = "Меланом се сматра најагресивнијим типом канцера коже. Услед иницијалне
или стечене резистенције и бројних нежељених дејстава, постојећи терапеутски
режими за метастатски меланом нису довољно ефикасни. Стога, меланом остаје
удружен са високом стопом смртности. Упркос опсежним терапеутским протоколима, стопа излечења инвазивних облика тумора је поражавајуће ниска те се
поставља питање шта је погрешно у актуленом приступу у онкотерапији. Главни критеријум за одабир нових антитуморских лекова превасходно је базиран
на њиховој способности да индукују апоптозу. Међутим, све више литературних
података доводе у везу агресивне терапеутске приступе који се базирају на индукцији апоптозе у туморима високог градуса, које карактерише присуство ћелија
слабо диферентованог фенотипа, са туморском прогресијом до које долази услед
компензаторне пролиферације. Решење проблема почива у повећању нивоа диференцијације тумора чиме ће опадати пролиферација индукована апоптозом.
Диферeнцијациона терапија представља нови концепт у терапији агресивних малигнитета. Многи диференцијациони агенси су природног порекла. У циљу повећања ефикасности и смањења токсичности конвенционалних терапија, стандардни терапеутски протоколи се често комбинују са комплементарном медицином,
где водећу позицију заузимају природни производи изоловани из биљака. Једну
од највећих и најразноврснијих класа секундарних биљних метаболита која се
одликује израженим антиканцерским потенцијалом представљају флавоноиди.
Пренилфлавоноиди из хмељa имају велики потенцијал да изазову промену малигног фенотипа у мирнији, функционално дефинисанији облик, ближи здравом
пандану истог или различитог ткива. Овакав приступ недовољно је истражен
чиме се отварају многе могућности како у научном тако и у комерцијалном смислу. Фокус овог предавања је стављен на пренилфлавоноид - изоксантохумол у
контексту евентуалне терапије меланома и креирања протокола који би подигли
ефикасност постојећих третмана комерцијалним хемотерапеутицима., Melanoma is considered the most aggressive type of skin cancer. Due to initial or
acquired resistance and numerous side effects, existing therapeutic regimens for metastatic
melanoma are not sufficiently effective. Therefore, melanoma remains associated with a
high mortality rate. Despite extensive therapeutic protocols, the curation rate for invasive
forms of tumors is quite low, and the question arises as to what is wrong with the current
approach in oncotherapy. The main criterion for the selection of new antitumor drugs is
primarily based on their ability to induce apoptosis. However, numerous literature data
link aggressive therapeutic approaches based on the induction of apoptosis in high grade
tumors, which are characterized by the presence of cells with a low-differentiated
phenotype, with tumor progression that occurs due to compensatory proliferation. The
solution to the problem lies in increasing the level of tumor differentiation, which will
decrease proliferation induced by apoptosis. Differentiation therapy represents a new
concept in the therapy of aggressive malignancies. Many differentiation agents are of
natural origin. In order to increase the efficacy and reduce the toxicity of conventional
therapies, standard therapeutic protocols are often combined with complementary
medicine, where the leading position is occupied by natural products isolated from
plants. Flavonoids are one of the largest and most diverse classes of secondary plant
metabolites, well-known for their pronounced anticancer potential. Prenylflavonoids
from the hop plant have a great potential to trigger a change of the malignant phenotype
into a quiescent, more functionally defined form, closer to the healthy counterpart of the
same or different tissue. This approach has mainly been unexplored, opening up many
possibilities in both scientific and commercial terms. The focus of this lecture will be
on prenylflavonoid - isoxanthohumol in the context of possible melanoma therapy and
the creation of protocols that would increase the effectiveness of existing conventional
chemotherapy.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Нутрацеутици хмеља у сусрет терапији метастатског меланома, Nutraceuticals from hops in the treatment of metastatic melanoma",
pages = "81-84",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6262"
}

Krajnović, T., Maksimović-Ivanić, D.,& Mijatović, S.. (2023). Нутрацеутици хмеља у сусрет терапији метастатског меланома. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 81-84.
https://hdl.handle.net/21.15107/rcub_ibiss_6262

Krajnović T, Maksimović-Ivanić D, Mijatović S. Нутрацеутици хмеља у сусрет терапији метастатског меланома. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:81-84.
https://hdl.handle.net/21.15107/rcub_ibiss_6262 .

Krajnović, Tamara, Maksimović-Ivanić, Danijela, Mijatović, Sanja, "Нутрацеутици хмеља у сусрет терапији метастатског меланома" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):81-84,
https://hdl.handle.net/21.15107/rcub_ibiss_6262 .

TY  - JOUR
AU  - Matija, Lidija R.
AU  - Stanković, Ivana M.
AU  - Purić, Milica
AU  - Miličić, Milica
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Gordić, Vuk
AU  - Koruga, Đuro Lj.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6426
AB  - The human body contains 60–70% water, depending on age. As a body fluid, it is not
only a medium in which physical and chemical processes take place, but it is also one of the active
mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by
themselves (in vacuum), are diamagnetic but when organized into clusters, they become diamagnetic
or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent
hydrogen bonds in their structure. The interaction, as well as signal transmission, between water
and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds,
which determine the state and dynamics of conformational changes in biomolecules. Disruptive
conformational changes in biomolecules, cells, and tissues lead to their dysfunctionality, so they are a
frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding
due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin
state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance
was developed based on the second derivative of the C60 molecule (SD-C60), which has classical and
quantum properties. The characterization of SD-C60 by UV-VIS-NIR, FTIR, TEM, and AFM/MFM
was performed and it is shown that SD-C60 water layers generate vibrations with near-zero phase
dispersion which are transmitted through Fibonacci’s water chains to biomolecules. In comparison
with previously published SD-C60 derivate (3HFWC, size until 10 nm, and 1–5 water layers), the
improved formulation (3HFWC-W, size 10–25 nm, and 6–9 water layers) showed multiplied cytotoxic
activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action
was preserved and based on an induction of senescence rather than cell death. Importantly, high
selectivity towards malignant phenotypes was detected. Observed effects can be ascribed to a
machinery of hydrogen bonds, which are generated in SD-C60 and transmitted through water to
biomolecules. This approach may open a new field in science and healthcare—a “water-based
nanomedicine”.
PB  - Basel: MDPI
T2  - Micromachines
T1  - The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine
IS  - 12
VL  - 14
DO  - 10.3390/mi14122152
SP  - 2152
ER  - 

@article{
author = "Matija, Lidija R. and Stanković, Ivana M. and Purić, Milica and Miličić, Milica and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Krajnović, Tamara and Gordić, Vuk and Koruga, Đuro Lj.",
year = "2023",
abstract = "The human body contains 60–70% water, depending on age. As a body fluid, it is not
only a medium in which physical and chemical processes take place, but it is also one of the active
mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by
themselves (in vacuum), are diamagnetic but when organized into clusters, they become diamagnetic
or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent
hydrogen bonds in their structure. The interaction, as well as signal transmission, between water
and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds,
which determine the state and dynamics of conformational changes in biomolecules. Disruptive
conformational changes in biomolecules, cells, and tissues lead to their dysfunctionality, so they are a
frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding
due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin
state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance
was developed based on the second derivative of the C60 molecule (SD-C60), which has classical and
quantum properties. The characterization of SD-C60 by UV-VIS-NIR, FTIR, TEM, and AFM/MFM
was performed and it is shown that SD-C60 water layers generate vibrations with near-zero phase
dispersion which are transmitted through Fibonacci’s water chains to biomolecules. In comparison
with previously published SD-C60 derivate (3HFWC, size until 10 nm, and 1–5 water layers), the
improved formulation (3HFWC-W, size 10–25 nm, and 6–9 water layers) showed multiplied cytotoxic
activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action
was preserved and based on an induction of senescence rather than cell death. Importantly, high
selectivity towards malignant phenotypes was detected. Observed effects can be ascribed to a
machinery of hydrogen bonds, which are generated in SD-C60 and transmitted through water to
biomolecules. This approach may open a new field in science and healthcare—a “water-based
nanomedicine”.",
publisher = "Basel: MDPI",
journal = "Micromachines",
title = "The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine",
number = "12",
volume = "14",
doi = "10.3390/mi14122152",
pages = "2152"
}

Matija, L. R., Stanković, I. M., Purić, M., Miličić, M., Maksimović-Ivanić, D., Mijatović, S., Krajnović, T., Gordić, V.,& Koruga, Đ. Lj.. (2023). The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine. in Micromachines
Basel: MDPI., 14(12), 2152.
https://doi.org/10.3390/mi14122152

Matija LR, Stanković IM, Purić M, Miličić M, Maksimović-Ivanić D, Mijatović S, Krajnović T, Gordić V, Koruga ĐL. The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine. in Micromachines. 2023;14(12):2152.
doi:10.3390/mi14122152 .

Matija, Lidija R., Stanković, Ivana M., Purić, Milica, Miličić, Milica, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Krajnović, Tamara, Gordić, Vuk, Koruga, Đuro Lj., "The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine" in Micromachines, 14, no. 12 (2023):2152,
https://doi.org/10.3390/mi14122152 . .

TY  - JOUR
AU  - Braun, Sebastian
AU  - Paskaš, Svetlana
AU  - Laube, Markus
AU  - George, Sven
AU  - Hofmann, Bettina
AU  - Lönnecke, Peter
AU  - Steinhilber, Dieter
AU  - Pietzsch, Jens
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6431
AB  - The presence of inflammatory mediators in the tumor microenvironment,
such as cytokines, growth factors or eicosanoids,
indicate cancer-related inflammatory processes. Targeting these
inflammatory mediators and related signal pathways may offer
a rational strategy for the treatment of cancer. This study
focuses on the incorporation of metabolically stable, sterically
demanding, and hydrophobic dicarba-closo-dodecaboranes
(carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase
(5-LO) inhibitors that are key enzymes in the biosynthesis
of eicosanoids. The di-tert-butylphenol derivative tebufelone
represents a selective dual COX-2/5-LO inhibitor. The incorporation
of meta- or para-carborane into the tebufelone scaffold
resulted in eight carborane-based tebufelone analogs that
show no COX inhibition but 5-LO inhibitory activity in vitro. Cell
viability studies on HT29 colon adenocarcinoma cells revealed
that the observed antiproliferative effect of the para-carborane
analogs of tebufelone is enhanced by structural modifications
that include chain elongation in combination with introduction
of a methylene spacer resulting in higher anticancer activity
compared to tebufelone. Hence, this strategy proved to be a
promising approach to design potent 5-LO inhibitors with
potential application as cytostatic agents.
PB  - Wiley-VCH GmbH
T2  - ChemMedChem
T1  - Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro
IS  - 14
VL  - 18
DO  - 10.1002/cmdc.202300206
SP  - e202300206
ER  - 

@article{
author = "Braun, Sebastian and Paskaš, Svetlana and Laube, Markus and George, Sven and Hofmann, Bettina and Lönnecke, Peter and Steinhilber, Dieter and Pietzsch, Jens and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The presence of inflammatory mediators in the tumor microenvironment,
such as cytokines, growth factors or eicosanoids,
indicate cancer-related inflammatory processes. Targeting these
inflammatory mediators and related signal pathways may offer
a rational strategy for the treatment of cancer. This study
focuses on the incorporation of metabolically stable, sterically
demanding, and hydrophobic dicarba-closo-dodecaboranes
(carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase
(5-LO) inhibitors that are key enzymes in the biosynthesis
of eicosanoids. The di-tert-butylphenol derivative tebufelone
represents a selective dual COX-2/5-LO inhibitor. The incorporation
of meta- or para-carborane into the tebufelone scaffold
resulted in eight carborane-based tebufelone analogs that
show no COX inhibition but 5-LO inhibitory activity in vitro. Cell
viability studies on HT29 colon adenocarcinoma cells revealed
that the observed antiproliferative effect of the para-carborane
analogs of tebufelone is enhanced by structural modifications
that include chain elongation in combination with introduction
of a methylene spacer resulting in higher anticancer activity
compared to tebufelone. Hence, this strategy proved to be a
promising approach to design potent 5-LO inhibitors with
potential application as cytostatic agents.",
publisher = "Wiley-VCH GmbH",
journal = "ChemMedChem",
title = "Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro",
number = "14",
volume = "18",
doi = "10.1002/cmdc.202300206",
pages = "e202300206"
}

Braun, S., Paskaš, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro. in ChemMedChem
Wiley-VCH GmbH., 18(14), e202300206.
https://doi.org/10.1002/cmdc.202300206

Braun S, Paskaš S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro. in ChemMedChem. 2023;18(14):e202300206.
doi:10.1002/cmdc.202300206 .

Braun, Sebastian, Paskaš, Svetlana, Laube, Markus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro" in ChemMedChem, 18, no. 14 (2023):e202300206,
https://doi.org/10.1002/cmdc.202300206 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Lönnecke, Peter
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6266
AB  - For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.
PB  - Royal Society of Chemistry
T2  - RSC Medicinal Chemistry
T1  - Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy
DO  - 10.1039/d3md00344b
ER  - 

@article{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.",
publisher = "Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy",
doi = "10.1039/d3md00344b"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry
Royal Society of Chemistry..
https://doi.org/10.1039/d3md00344b

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry. 2023;.
doi:10.1039/d3md00344b .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy" in RSC Medicinal Chemistry (2023),
https://doi.org/10.1039/d3md00344b . .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6267
AB  - Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells
SP  - 98
EP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6267
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells",
pages = "98-99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6267"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):98-99,
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

TY  - JOUR
AU  - Richter, Stefan
AU  - Lönnecke, Peter
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6265
AB  - The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.
PB  - Belgrade: Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives
DO  - 10.2298/JSC230818072R
ER  - 

@article{
author = "Richter, Stefan and Lönnecke, Peter and Bovan, Dijana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives",
doi = "10.2298/JSC230818072R"
}

Richter, S., Lönnecke, P., Bovan, D., Mijatović, S., Maksimović-Ivanić, D., Kaluđerović, G. N.,& Hey-Hawkins, E.. (2023). Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society
Belgrade: Serbian Chemical Society..
https://doi.org/10.2298/JSC230818072R

Richter S, Lönnecke P, Bovan D, Mijatović S, Maksimović-Ivanić D, Kaluđerović GN, Hey-Hawkins E. Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society. 2023;.
doi:10.2298/JSC230818072R .

Richter, Stefan, Lönnecke, Peter, Bovan, Dijana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives" in Journal of the Serbian Chemical Society (2023),
https://doi.org/10.2298/JSC230818072R . .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandr
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6261
AB  - Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула.
AB  - Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке
T1  - Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment
SP  - 18
EP  - 19
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6261
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandr and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула., Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке, Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment",
pages = "18-19",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6261"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

Murganić, Blagoje, Kazimir, Aleksandr, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):18-19,
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Braun, Sebastian
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6260
AB  - Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo.
AB  - Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана
T1  - In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6260
ER  - 

@conference{
author = "Jelača, Sanja and Braun, Sebastian and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo., Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана, In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6260"
}

Jelača, S., Braun, S., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260

Jelača S, Braun S, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

Jelača, Sanja, Braun, Sebastian, Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Useini, Liridona
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6259
AB  - Нестероидни антиинфламаторни лекови (НСАИЛ) у које између осталог
спада нимесулид показали су антитуморски ефекат против различитих типо-
ва туморских ћелијских линија. Потенцијални цитотоксични ефекат изониме-
сулида, члана породице нимесулида, и његових деривата карборана одређен је
на HT29, HCT116, MCF-7, А375 и А549 хуманим ћелијским линијама. Вијабил-
ност свих тестираних ћелијских линија је дозно-зависно смањена, што је по-
казано МТТ и CV тестовима. Селективност ових једињења према туморском
фенотипу је показана на МRC-5 ћелијама и ћелијама перитонеалног ексудата
мишa, под идентичним експерименталним условима. Проточна цитофлуото-
метријска анализа је открила значајно смањење деобног потенцијала МCF-7
ћелија, након третмана изонимесулидом и његовим одабраним дериватима
карборана (4а и 4б). Показано је да су карборански деривати изонимесулида
изазвали снажну апоптозу која није била посредована активацијом каспазе.
Са друге стране, изонимесулид је покренуо апоптозу посредовану активаци-
јом каспаза и смањио пролиферацију знатно нижом стопом од његових кар-
боранскх деривата. У даљем истраживању апоптозу потврђујемо пропидијум
јодид бојењем МCF-7 ћелија применом флуоресцентне микроскопије. Код
третираних ћелија уочавамо интензивну апоптозу која се манифестује непра-
вилним обликом једара и кондензацијом хроматина. Коначно, инхибирана
производња реактивних врста кисеоника и азота примећена је само у случају
деривата 4б. Нове карактеристике изонимесулида и његових деривата карбо-
рана огледају се у њиховом снажном антитуморном потенцијалу, што отвара
бројне могућности за даља истраживања.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as nimesulide have shown
antitumor effects against different types of tumor cell lines. The potential cytotoxic effect
of isonimesulide, a member of the nimesulide family, and its carborane derivatives
was determined against HT29, HCT116, MCF-7, A375, and A549 human cell lines. The
viability of all tested cell lines was dose-dependently decreased as shown by 3-(4,5-dimethythiazol-
2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. The selectivity
of these compounds toward a tumor phenotype was demonstrated on MRC-5
and peritoneal exudate cells under identical experimental conditions. Flow cytometric
analysis revealed a significant reduction in the division potential of MCF-7 cells treated
with isonimesulide and two selected carborane derivatives (4a and 4b). Subsequently,
isonimesulide carborane derivatives induced strong apoptosis which was not mediated by
caspase activation. On the other hand, isonimesulide initiated caspase-mediated apoptosis
and reduced proliferation at a significantly lower rate than its carborane derivatives. In
further investigations, intensive apoptosis manifested with the irregular shape of nuclei,
and chromatin condensation was confirmed by propidium iodide (PI) staining of treated
MCF-7 cells using fluorescent microscopy. Finally, the inhibited production of reactive
oxygen and nitrogen species (ROS/RNS) was observed only in the case of 4b. The new features
of isonimesulide and its carborane derivatives are reflected in their strong antitumor
potential, which opens numerous possibilities for further research.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Aнтитуморски потенцијал изонимесулида и његових деривата карборана
T1  - Antitumor potential of isonimesulide and its carborane derivatives
SP  - 85
EP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6259
ER  - 

@conference{
author = "Komazec, Teodora and Useini, Liridona and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Нестероидни антиинфламаторни лекови (НСАИЛ) у које између осталог
спада нимесулид показали су антитуморски ефекат против различитих типо-
ва туморских ћелијских линија. Потенцијални цитотоксични ефекат изониме-
сулида, члана породице нимесулида, и његових деривата карборана одређен је
на HT29, HCT116, MCF-7, А375 и А549 хуманим ћелијским линијама. Вијабил-
ност свих тестираних ћелијских линија је дозно-зависно смањена, што је по-
казано МТТ и CV тестовима. Селективност ових једињења према туморском
фенотипу је показана на МRC-5 ћелијама и ћелијама перитонеалног ексудата
мишa, под идентичним експерименталним условима. Проточна цитофлуото-
метријска анализа је открила значајно смањење деобног потенцијала МCF-7
ћелија, након третмана изонимесулидом и његовим одабраним дериватима
карборана (4а и 4б). Показано је да су карборански деривати изонимесулида
изазвали снажну апоптозу која није била посредована активацијом каспазе.
Са друге стране, изонимесулид је покренуо апоптозу посредовану активаци-
јом каспаза и смањио пролиферацију знатно нижом стопом од његових кар-
боранскх деривата. У даљем истраживању апоптозу потврђујемо пропидијум
јодид бојењем МCF-7 ћелија применом флуоресцентне микроскопије. Код
третираних ћелија уочавамо интензивну апоптозу која се манифестује непра-
вилним обликом једара и кондензацијом хроматина. Коначно, инхибирана
производња реактивних врста кисеоника и азота примећена је само у случају
деривата 4б. Нове карактеристике изонимесулида и његових деривата карбо-
рана огледају се у њиховом снажном антитуморном потенцијалу, што отвара
бројне могућности за даља истраживања., Nonsteroidal anti-inflammatory drugs (NSAIDs) such as nimesulide have shown
antitumor effects against different types of tumor cell lines. The potential cytotoxic effect
of isonimesulide, a member of the nimesulide family, and its carborane derivatives
was determined against HT29, HCT116, MCF-7, A375, and A549 human cell lines. The
viability of all tested cell lines was dose-dependently decreased as shown by 3-(4,5-dimethythiazol-
2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. The selectivity
of these compounds toward a tumor phenotype was demonstrated on MRC-5
and peritoneal exudate cells under identical experimental conditions. Flow cytometric
analysis revealed a significant reduction in the division potential of MCF-7 cells treated
with isonimesulide and two selected carborane derivatives (4a and 4b). Subsequently,
isonimesulide carborane derivatives induced strong apoptosis which was not mediated by
caspase activation. On the other hand, isonimesulide initiated caspase-mediated apoptosis
and reduced proliferation at a significantly lower rate than its carborane derivatives. In
further investigations, intensive apoptosis manifested with the irregular shape of nuclei,
and chromatin condensation was confirmed by propidium iodide (PI) staining of treated
MCF-7 cells using fluorescent microscopy. Finally, the inhibited production of reactive
oxygen and nitrogen species (ROS/RNS) was observed only in the case of 4b. The new features
of isonimesulide and its carborane derivatives are reflected in their strong antitumor
potential, which opens numerous possibilities for further research.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Aнтитуморски потенцијал изонимесулида и његових деривата карборана, Antitumor potential of isonimesulide and its carborane derivatives",
pages = "85-87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6259"
}

Komazec, T., Useini, L., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Aнтитуморски потенцијал изонимесулида и његових деривата карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 85-87.
https://hdl.handle.net/21.15107/rcub_ibiss_6259

Komazec T, Useini L, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Aнтитуморски потенцијал изонимесулида и његових деривата карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:85-87.
https://hdl.handle.net/21.15107/rcub_ibiss_6259 .

Komazec, Teodora, Useini, Liridona, Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Aнтитуморски потенцијал изонимесулида и његових деривата карборана" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):85-87,
https://hdl.handle.net/21.15107/rcub_ibiss_6259 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Kasalović, Marijana P.
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6239
AB  - Background: The limited efficacy of conventional metal-based chemotherapeutic drugs is attributed to resistance, high toxicity, and numerous side effects, thus providing a platform for design of new metal-based drugs with enhanced properties. Organotin(IV) compounds have already been recognized as promising agents due to their ability to inhibit tumor growth both in in vitro and in vivo. Following this concept, new diphenyltin(IV) complexes incorporating carboxylato N-functionalized 2-quinolones ligands were assessed on different cancer cell lines. Material and Methods: Evaluation of anticancer activity in vitro of the newly synthesized diphenyltin(IV)complexes bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-l)propanoato)diphenyltin(IV), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV)  (1−3, respectively) as well as ligand precursors (HL1, HL2, and HL3) was determined after 72 h on a panel of cancer cell lines of human and mouse origin (MCF-7, A375, HCT116, 4T1, B16, CT26) using MTT and CV assays. Complex 1 and HCT116 cells were selected for further analysis of the potential mechanism, Flow cytometry for the assessment of cell death, proliferation, caspase activation and production of active oxygen/nitrogen species as well as fluorescent microscopy for detection of nuclei morphology were employed. Results: Obtained results showed a dose-dependent viability decrease in all cell lines exposed to complexes 1−3 with IC50 values in the low micromolar range. Ligand precursors, HL1−HL3 showed no activity up to 200 μM. Complex 1 inhibited cell proliferation and provoked caspase-dependent apoptosis in HCT116 cells. The enhanced presence of autophagosomes determined after the treatment with complex 1 was found to be protective, opposing to apoptosis. The scavenging potential of tested complex 1 on ROS/RNS production can be connected with abolished viability and suppressed proliferation, since HCT116 cells are potent producers of ROS. Conclusions: Taking all together, novel diphenyltin(IV) complexes present promising anticancer agents and should be further tested in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6239
ER  - 

@conference{
author = "Jelača, Sanja and Kasalović, Marijana P. and Pantelić, Nebojša Đ. and Kaluđerović, Goran N. and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: The limited efficacy of conventional metal-based chemotherapeutic drugs is attributed to resistance, high toxicity, and numerous side effects, thus providing a platform for design of new metal-based drugs with enhanced properties. Organotin(IV) compounds have already been recognized as promising agents due to their ability to inhibit tumor growth both in in vitro and in vivo. Following this concept, new diphenyltin(IV) complexes incorporating carboxylato N-functionalized 2-quinolones ligands were assessed on different cancer cell lines. Material and Methods: Evaluation of anticancer activity in vitro of the newly synthesized diphenyltin(IV)complexes bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-l)propanoato)diphenyltin(IV), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV)  (1−3, respectively) as well as ligand precursors (HL1, HL2, and HL3) was determined after 72 h on a panel of cancer cell lines of human and mouse origin (MCF-7, A375, HCT116, 4T1, B16, CT26) using MTT and CV assays. Complex 1 and HCT116 cells were selected for further analysis of the potential mechanism, Flow cytometry for the assessment of cell death, proliferation, caspase activation and production of active oxygen/nitrogen species as well as fluorescent microscopy for detection of nuclei morphology were employed. Results: Obtained results showed a dose-dependent viability decrease in all cell lines exposed to complexes 1−3 with IC50 values in the low micromolar range. Ligand precursors, HL1−HL3 showed no activity up to 200 μM. Complex 1 inhibited cell proliferation and provoked caspase-dependent apoptosis in HCT116 cells. The enhanced presence of autophagosomes determined after the treatment with complex 1 was found to be protective, opposing to apoptosis. The scavenging potential of tested complex 1 on ROS/RNS production can be connected with abolished viability and suppressed proliferation, since HCT116 cells are potent producers of ROS. Conclusions: Taking all together, novel diphenyltin(IV) complexes present promising anticancer agents and should be further tested in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6239"
}

Jelača, S., Kasalović, M. P., Pantelić, N. Đ., Kaluđerović, G. N., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_6239

Jelača S, Kasalović MP, Pantelić NĐ, Kaluđerović GN, Mijatović S, Maksimović-Ivanić D. Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:100.
https://hdl.handle.net/21.15107/rcub_ibiss_6239 .

Jelača, Sanja, Kasalović, Marijana P., Pantelić, Nebojša Đ., Kaluđerović, Goran N., Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):100,
https://hdl.handle.net/21.15107/rcub_ibiss_6239 .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandar
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6244
AB  - Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6244
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6244"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

Murganić, Blagoje, Kazimir, Aleksandar, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mihajlović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6237
AB  - Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells
SP  - 96
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6237
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mihajlović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells",
pages = "96",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6237"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mihajlović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mihajlović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mihajlović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells" in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):96,
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Kasalović, Marijana P.
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6236
AB  - Cancer is responsible for millions of deaths worldwide each year and, although great
advances have been made in the treatment options, there are still many issues that must be
addressed in order to improve cancer therapy. In the present work, anticancer effect of
three novel Ph3 SnL complexes (L1 –,3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato;
L2 –,2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato; L3 –,2-(4-hydroxy-2-oxoquinolin-
1(2H)-yl)ethanoato), was evaluated against several cancer cell lines (MCA-7, A375,
HCT116, 4T1, B16 and CT26). The applied treatment decreased cell viability of all cell
lines after 72 h in a dose-dependent manner with IC50 values in the low micromolar range.
Flow cytometric assessment revealed apoptotic cell death in A375 but not B16 culture,
exposed to tested drug. Morphological signs of apoptosis such as shrunk nuclei and
condensed chromatin were further confirmed by fluorescent microscopy. Same treatment
in B16 lead to cell division block coupled with two-fold increase in the amount of melanin
and tyrosinase activity, indicating the differentiation of B16 cells towards melanocytes. In
the background of different response of two melanoma cell lines lies dissimilar redox
response to the treatment. While in A375 cultures, ROS/RNS production is inhibited in
comparison to control, in B16 cells compound Ph3SnL1 provokes ROS/RNS generation.
Finally, when applied in therapeutic regiment, Ph3SnL1 significantly reduced tumor
volume in C57BL/6 mice.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6236
ER  - 

@conference{
author = "Jelača, Sanja and Kasalović, Marijana P. and Pantelić, Nebojša Đ. and Kaluđerović, Goran N. and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Cancer is responsible for millions of deaths worldwide each year and, although great
advances have been made in the treatment options, there are still many issues that must be
addressed in order to improve cancer therapy. In the present work, anticancer effect of
three novel Ph3 SnL complexes (L1 –,3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato;
L2 –,2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato; L3 –,2-(4-hydroxy-2-oxoquinolin-
1(2H)-yl)ethanoato), was evaluated against several cancer cell lines (MCA-7, A375,
HCT116, 4T1, B16 and CT26). The applied treatment decreased cell viability of all cell
lines after 72 h in a dose-dependent manner with IC50 values in the low micromolar range.
Flow cytometric assessment revealed apoptotic cell death in A375 but not B16 culture,
exposed to tested drug. Morphological signs of apoptosis such as shrunk nuclei and
condensed chromatin were further confirmed by fluorescent microscopy. Same treatment
in B16 lead to cell division block coupled with two-fold increase in the amount of melanin
and tyrosinase activity, indicating the differentiation of B16 cells towards melanocytes. In
the background of different response of two melanoma cell lines lies dissimilar redox
response to the treatment. While in A375 cultures, ROS/RNS production is inhibited in
comparison to control, in B16 cells compound Ph3SnL1 provokes ROS/RNS generation.
Finally, when applied in therapeutic regiment, Ph3SnL1 significantly reduced tumor
volume in C57BL/6 mice.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6236"
}

Jelača, S., Kasalović, M. P., Pantelić, N. Đ., Kaluđerović, G. N., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6236

Jelača S, Kasalović MP, Pantelić NĐ, Kaluđerović GN, Mijatović S, Maksimović-Ivanić D. Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6236 .

Jelača, Sanja, Kasalović, Marijana P., Pantelić, Nebojša Đ., Kaluđerović, Goran N., Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6236 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Jelača, Sanja
AU  - Biancalana, Lorenzo
AU  - Chiaverini, Lorenzo
AU  - Mijatović, Sanja
AU  - Zacchini, Stefano
AU  - Marchetti, Fabio
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6219
AB  - Лекови на бази метала се деценијама користе у терапији рака. Нажалост, њихова ефикасност је обично праћена значајном токсичношћу и због тога постоји стална потреба за развојем лекова са побољшаним безбедносним профилом. Гвожђе је важан елемент са строго регулисаним метаболизмом и игра кључну улогу у многим физиолошким процесима у организму, попут раста и развоја, што је посебно важно када су у питању ћелије рака. Пошто имају повећане потребе за гвожђем у односу на здраве ћелије, може се очекивати да ћелије рака буду осетљивије на третман једињењима гвожђа од здравих ћелија. У овој студији, испитан је цитотоксични ефекат бинуклеарних једињења гвожђа са изоцијанидним лигандом (Xyl-NC, XylNC+DMAP, Ind-NC) на ћелијама рака хуманог порекла: А2780 рак јајника, MCF-7 рак дојке и HCT116 колоректални карцином in vitro. Третман испитиваним једињењима је смањио вијабилитет свих ћелија рака, док су А2780 одабране за даље истраживање као најосетљивије. Показало се да третман ћелија рака јајника бинуклеарним једињењима гвожђа са изоцијандним лигандима индукује фероптозу, ћелијску смрт изазвану липидном пероксидацијом зависном од гвожђа. Изненађујуће, фероптоза је праћена инхибицијом продукције радикала који узрокују оксидативни и нитрозативни стрес - водоник пероксида и пероксинитрита. Поред тога, показало се да третман свим једињењима узрокује аутофагију ћелија рака јајника. Третман у комбинацији са инхибитором аутофагије 3-метил аденином додатно смањује вијабилитет ћелија, што сугерише да детектована аутофагија има цитопротективну улогу. Такође, третман испитиваним једињењима значајно је инхибирао пролиферацију ћелија рака јајника. Резултати добијени у овој студији указују да би бинуклеарна једињења гвожђа са изоцијанидним лигандима могла постати обећавајући агенси за лечење рака и стога захтевају додатну пажњу и детаљнија биолошка истраживања
AB  - Metal-based drugs have been used as cancer therapeutics for decades. Unfortunately, their efficacy usually comes with significant toxicity and there is a constant need for the development of drugs with improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial role in many physiological processes in the body, like growth and development, which is particularly important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected that they could be more susceptible to treatment with iron compounds than healthy cells. In the present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP, Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis, cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite. Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide ligands could become promising agents for cancer treatment and therefore, require additional attention and further biological assessment.
improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial
role in many physiological processes in the body, like growth and development, which is particularly
important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected
that they could be more susceptible to treatment with iron compounds than healthy cells. In the
present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP,
Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and
HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability
of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was
shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis,
cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by
the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite.
Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy
inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide
ligands could become promising agents for cancer treatment and therefore, require additional attention
and further biological assessment.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом
T1  - Antitumor potential of diiron compounds with isocyanide ligands
SP  - 32
EP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6219
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Jelača, Sanja and Biancalana, Lorenzo and Chiaverini, Lorenzo and Mijatović, Sanja and Zacchini, Stefano and Marchetti, Fabio and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Лекови на бази метала се деценијама користе у терапији рака. Нажалост, њихова ефикасност је обично праћена значајном токсичношћу и због тога постоји стална потреба за развојем лекова са побољшаним безбедносним профилом. Гвожђе је важан елемент са строго регулисаним метаболизмом и игра кључну улогу у многим физиолошким процесима у организму, попут раста и развоја, што је посебно важно када су у питању ћелије рака. Пошто имају повећане потребе за гвожђем у односу на здраве ћелије, може се очекивати да ћелије рака буду осетљивије на третман једињењима гвожђа од здравих ћелија. У овој студији, испитан је цитотоксични ефекат бинуклеарних једињења гвожђа са изоцијанидним лигандом (Xyl-NC, XylNC+DMAP, Ind-NC) на ћелијама рака хуманог порекла: А2780 рак јајника, MCF-7 рак дојке и HCT116 колоректални карцином in vitro. Третман испитиваним једињењима је смањио вијабилитет свих ћелија рака, док су А2780 одабране за даље истраживање као најосетљивије. Показало се да третман ћелија рака јајника бинуклеарним једињењима гвожђа са изоцијандним лигандима индукује фероптозу, ћелијску смрт изазвану липидном пероксидацијом зависном од гвожђа. Изненађујуће, фероптоза је праћена инхибицијом продукције радикала који узрокују оксидативни и нитрозативни стрес - водоник пероксида и пероксинитрита. Поред тога, показало се да третман свим једињењима узрокује аутофагију ћелија рака јајника. Третман у комбинацији са инхибитором аутофагије 3-метил аденином додатно смањује вијабилитет ћелија, што сугерише да детектована аутофагија има цитопротективну улогу. Такође, третман испитиваним једињењима значајно је инхибирао пролиферацију ћелија рака јајника. Резултати добијени у овој студији указују да би бинуклеарна једињења гвожђа са изоцијанидним лигандима могла постати обећавајући агенси за лечење рака и стога захтевају додатну пажњу и детаљнија биолошка истраживања, Metal-based drugs have been used as cancer therapeutics for decades. Unfortunately, their efficacy usually comes with significant toxicity and there is a constant need for the development of drugs with improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial role in many physiological processes in the body, like growth and development, which is particularly important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected that they could be more susceptible to treatment with iron compounds than healthy cells. In the present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP, Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis, cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite. Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide ligands could become promising agents for cancer treatment and therefore, require additional attention and further biological assessment.
improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial
role in many physiological processes in the body, like growth and development, which is particularly
important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected
that they could be more susceptible to treatment with iron compounds than healthy cells. In the
present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP,
Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and
HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability
of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was
shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis,
cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by
the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite.
Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy
inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide
ligands could become promising agents for cancer treatment and therefore, require additional attention
and further biological assessment.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом, Antitumor potential of diiron compounds with isocyanide ligands",
pages = "32-33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6219"
}

Mihajlović, E., Jelača, S., Biancalana, L., Chiaverini, L., Mijatović, S., Zacchini, S., Marchetti, F.,& Maksimović-Ivanić, D.. (2023). Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 32-33.
https://hdl.handle.net/21.15107/rcub_ibiss_6219

Mihajlović E, Jelača S, Biancalana L, Chiaverini L, Mijatović S, Zacchini S, Marchetti F, Maksimović-Ivanić D. Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:32-33.
https://hdl.handle.net/21.15107/rcub_ibiss_6219 .

Mihajlović, Ekatarina, Jelača, Sanja, Biancalana, Lorenzo, Chiaverini, Lorenzo, Mijatović, Sanja, Zacchini, Stefano, Marchetti, Fabio, Maksimović-Ivanić, Danijela, "Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):32-33,
https://hdl.handle.net/21.15107/rcub_ibiss_6219 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Jelača, Sanja
AU  - Biancalana, Lorenzo
AU  - Chiaverini, Lorenzo
AU  - Mijatović, Sanja
AU  - Zacchini, Stefano
AU  - Marchetti, Fabio
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6218
AB  - Background: Iron is an important trace element with a broad range of functions in diverse physiological processes and tightly regulated metabolism. Over the years, numerous studies have indicated that cancer cells exhibit an iron-seeking phenotype, meaning they have higher demands for iron than healthy cells. This feature may serve as a foundation for a new approach to cancer therapy. In order to develop anticancer drug with improved efficacy, higher selectivity and reduced toxicity, a new organo-diiron complex with a bridging thiocarbyne ligand (FeSDAP) was synthesized. Material and Methods: The cytotoxic effect of FeSDAP was investigated on mouse cancer cell lines (B16-F1 low-invasive melanoma, B16-F10 high-invasive melanoma and 4T1 breast cancer), as well as on mouse embryonic fibroblasts (NIH-3T3). For investigation of its mechanism of action, flow cytometry and light microscopy were used. To investigate how 72h long exposure to DMAP in vitro affect the potential of B16-F1 and B16-F10 cells to form tumor in vivo, respective subcutaneous synegenic models in C57BL/6 mice were used. Results and Conclusions: Treatment with FeSDAP decreased viability of all cells after 72 hours, with significantly less potent effect on embryionic fibroblasts compared to cancer cells, suggesting FeSDAP may possess selectivity towards malignant phenotype. Melanoma cells were almost equally sensitive to the treatment, but more sensitive than breast cancer cells, so both B16-F1 and B16-F10 were selected for further comparative investigation. Treatment with FeSDAP inhibited proliferation of melanoma cells and caused substantial change in their morphology, which was even more pronounced when it comes to B16-F10 cells. After microscopic evaluation, it was shown that melanoma cells went into senescence. Prominent morphological change of B16-F10 cells was caused by transdifferentiation into Schwann Cell-Like Cells. Further investigation of tumorigenic potential of treated melanoma cells in mice showed that the average tumor size in the groups that received treated cells was significantly smaller, suggesting that melanoma cells have persistently reduced potential to form tumor after single in vitro treatment with FeSDAP. Ultimately, these results strongly indicate that investigated diiron thiocarbyne complexes may display a promising antitumor potential that will be investigated in more detail.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The effect of diiron thiocarbyne complex on tumor cells of different grade
SP  - 61
EP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6218
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Jelača, Sanja and Biancalana, Lorenzo and Chiaverini, Lorenzo and Mijatović, Sanja and Zacchini, Stefano and Marchetti, Fabio and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Iron is an important trace element with a broad range of functions in diverse physiological processes and tightly regulated metabolism. Over the years, numerous studies have indicated that cancer cells exhibit an iron-seeking phenotype, meaning they have higher demands for iron than healthy cells. This feature may serve as a foundation for a new approach to cancer therapy. In order to develop anticancer drug with improved efficacy, higher selectivity and reduced toxicity, a new organo-diiron complex with a bridging thiocarbyne ligand (FeSDAP) was synthesized. Material and Methods: The cytotoxic effect of FeSDAP was investigated on mouse cancer cell lines (B16-F1 low-invasive melanoma, B16-F10 high-invasive melanoma and 4T1 breast cancer), as well as on mouse embryonic fibroblasts (NIH-3T3). For investigation of its mechanism of action, flow cytometry and light microscopy were used. To investigate how 72h long exposure to DMAP in vitro affect the potential of B16-F1 and B16-F10 cells to form tumor in vivo, respective subcutaneous synegenic models in C57BL/6 mice were used. Results and Conclusions: Treatment with FeSDAP decreased viability of all cells after 72 hours, with significantly less potent effect on embryionic fibroblasts compared to cancer cells, suggesting FeSDAP may possess selectivity towards malignant phenotype. Melanoma cells were almost equally sensitive to the treatment, but more sensitive than breast cancer cells, so both B16-F1 and B16-F10 were selected for further comparative investigation. Treatment with FeSDAP inhibited proliferation of melanoma cells and caused substantial change in their morphology, which was even more pronounced when it comes to B16-F10 cells. After microscopic evaluation, it was shown that melanoma cells went into senescence. Prominent morphological change of B16-F10 cells was caused by transdifferentiation into Schwann Cell-Like Cells. Further investigation of tumorigenic potential of treated melanoma cells in mice showed that the average tumor size in the groups that received treated cells was significantly smaller, suggesting that melanoma cells have persistently reduced potential to form tumor after single in vitro treatment with FeSDAP. Ultimately, these results strongly indicate that investigated diiron thiocarbyne complexes may display a promising antitumor potential that will be investigated in more detail.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The effect of diiron thiocarbyne complex on tumor cells of different grade",
pages = "61-62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6218"
}

Mihajlović, E., Jelača, S., Biancalana, L., Chiaverini, L., Mijatović, S., Zacchini, S., Marchetti, F.,& Maksimović-Ivanić, D.. (2023). The effect of diiron thiocarbyne complex on tumor cells of different grade. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 61-62.
https://hdl.handle.net/21.15107/rcub_ibiss_6218

Mihajlović E, Jelača S, Biancalana L, Chiaverini L, Mijatović S, Zacchini S, Marchetti F, Maksimović-Ivanić D. The effect of diiron thiocarbyne complex on tumor cells of different grade. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:61-62.
https://hdl.handle.net/21.15107/rcub_ibiss_6218 .

Mihajlović, Ekatarina, Jelača, Sanja, Biancalana, Lorenzo, Chiaverini, Lorenzo, Mijatović, Sanja, Zacchini, Stefano, Marchetti, Fabio, Maksimović-Ivanić, Danijela, "The effect of diiron thiocarbyne complex on tumor cells of different grade" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):61-62,
https://hdl.handle.net/21.15107/rcub_ibiss_6218 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - https://www.sdir.ac.rs/oncology-insights/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6215
AB  - Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6215
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Hey-Hawkins, Evamarie and Kaluđerović, Goran N. and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6215"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Hey-Hawkins, E., Kaluđerović, G. N.,& Maksimović-Ivanić, D.. (2023). The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Hey-Hawkins E, Kaluđerović GN, Maksimović-Ivanić D. The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., Maksimović-Ivanić, Danijela, "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):62,
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6217
AB  - Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model
SP  - 97
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6217
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model",
pages = "97-98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6217"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):97-98,
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .