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  - 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  - 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 .

TY  - JOUR
AU  - Useini, Liridona
AU  - Komazec, Teodora
AU  - Laube, Markus
AU  - Lönnecke, Peter
AU  - Schädlich, Jonas
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Pietzsch, Jens
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5826
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used
therapeutics against pain, fever, and inflammation; additionally, antitumor
properties are reported. NSAIDs reduce the synthesis of prostaglandins by
inhibiting the cyclooxygenase (COX) isoforms COX-1 and COX-2. As
nonselective inhibition is associated with off-target effects, strategies to
achieve selectivity for the clinically preferred isoform COX-2 are of high
interest. The modification of NSAIDs using carborane clusters as phenyl
mimetics is reported to alter the selectivity profile through size exclusion.
Inspired by these findings, isonimesulide and its carborane derivatives are
prepared. The biological screening shows that the carborane containing
compounds exhibit a stronger antitumor potential compared to nimesulide
and isonimesulide. Furthermore, the replacement of the phenyl ring of
isonimesulide with a carborane moiety resulted in a shift of the COX activity
from nonactive to COX-active compounds.
PB  - Hoboken: Wiley
T2  - Advanced Therapeutics
T1  - Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents
DO  - 10.1002/adtp.202300117
SP  - 2300117
ER  - 

@article{
author = "Useini, Liridona and Komazec, Teodora and Laube, Markus and Lönnecke, Peter and Schädlich, Jonas and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Pietzsch, Jens and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used
therapeutics against pain, fever, and inflammation; additionally, antitumor
properties are reported. NSAIDs reduce the synthesis of prostaglandins by
inhibiting the cyclooxygenase (COX) isoforms COX-1 and COX-2. As
nonselective inhibition is associated with off-target effects, strategies to
achieve selectivity for the clinically preferred isoform COX-2 are of high
interest. The modification of NSAIDs using carborane clusters as phenyl
mimetics is reported to alter the selectivity profile through size exclusion.
Inspired by these findings, isonimesulide and its carborane derivatives are
prepared. The biological screening shows that the carborane containing
compounds exhibit a stronger antitumor potential compared to nimesulide
and isonimesulide. Furthermore, the replacement of the phenyl ring of
isonimesulide with a carborane moiety resulted in a shift of the COX activity
from nonactive to COX-active compounds.",
publisher = "Hoboken: Wiley",
journal = "Advanced Therapeutics",
title = "Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents",
doi = "10.1002/adtp.202300117",
pages = "2300117"
}

Useini, L., Komazec, T., Laube, M., Lönnecke, P., Schädlich, J., Mijatović, S., Maksimović-Ivanić, D., Pietzsch, J.,& Hey-Hawkins, E.. (2023). Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents. in Advanced Therapeutics
Hoboken: Wiley., 2300117.
https://doi.org/10.1002/adtp.202300117

Useini L, Komazec T, Laube M, Lönnecke P, Schädlich J, Mijatović S, Maksimović-Ivanić D, Pietzsch J, Hey-Hawkins E. Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents. in Advanced Therapeutics. 2023;:2300117.
doi:10.1002/adtp.202300117 .

Useini, Liridona, Komazec, Teodora, Laube, Markus, Lönnecke, Peter, Schädlich, Jonas, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Pietzsch, Jens, Hey-Hawkins, Evamarie, "Isonimesulide and Its Carborane Analogues as Isoform-Selective COX Inhibitors and Antitumor Agents" in Advanced Therapeutics (2023):2300117,
https://doi.org/10.1002/adtp.202300117 . .

TY  - JOUR
AU  - Predarska, Ivana
AU  - Saoud, Mohamad
AU  - Drača, Dijana
AU  - Morgan, Ibrahim
AU  - Komazec, Teodora
AU  - Eichhorn, Thomas
AU  - Mihajlović, Ekatarina
AU  - Dunđerović, Duško
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5238
AB  - The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
IS  - 21
VL  - 12
DO  - 10.3390/nano12213767
SP  - 3767
ER  - 

@article{
author = "Predarska, Ivana and Saoud, Mohamad and Drača, Dijana and Morgan, Ibrahim and Komazec, Teodora and Eichhorn, Thomas and Mihajlović, Ekatarina and Dunđerović, Duško and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie and Kaluđerović, Goran N.",
year = "2022",
abstract = "The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines",
number = "21",
volume = "12",
doi = "10.3390/nano12213767",
pages = "3767"
}

Predarska, I., Saoud, M., Drača, D., Morgan, I., Komazec, T., Eichhorn, T., Mihajlović, E., Dunđerović, D., Mijatović, S., Maksimović-Ivanić, D., Hey-Hawkins, E.,& Kaluđerović, G. N.. (2022). Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials
Basel: MDPI., 12(21), 3767.
https://doi.org/10.3390/nano12213767

Predarska I, Saoud M, Drača D, Morgan I, Komazec T, Eichhorn T, Mihajlović E, Dunđerović D, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E, Kaluđerović GN. Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials. 2022;12(21):3767.
doi:10.3390/nano12213767 .

Predarska, Ivana, Saoud, Mohamad, Drača, Dijana, Morgan, Ibrahim, Komazec, Teodora, Eichhorn, Thomas, Mihajlović, Ekatarina, Dunđerović, Duško, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines" in Nanomaterials, 12, no. 21 (2022):3767,
https://doi.org/10.3390/nano12213767 . .

TY  - CONF
AU  - Drača, Dijana
AU  - Predarska, Ivana
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5288
AB  - Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5288
ER  - 

@conference{
author = "Drača, Dijana and Predarska, Ivana and Komazec, Teodora and Mihajlović, Ekatarina and Kaluđerović, Goran N. and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5288"
}

Drača, D., Predarska, I., Komazec, T., Mihajlović, E., Kaluđerović, G. N., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288

Drača D, Predarska I, Komazec T, Mihajlović E, Kaluđerović GN, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

Drača, Dijana, Predarska, Ivana, Komazec, Teodora, Mihajlović, Ekatarina, Kaluđerović, Goran N., Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):62,
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Drača, Dijana
AU  - Komazec, Teodora
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5287
AB  - To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5287
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Drača, Dijana and Komazec, Teodora and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15",
pages = "99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5287"
}

Mihajlović, E., Drača, D., Komazec, T., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287

Mihajlović E, Drača D, Komazec T, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

Mihajlović, Ekatarina, Drača, Dijana, Komazec, Teodora, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):99,
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5284
AB  - From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines
SP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5284
ER  - 

@conference{
author = "Komazec, Teodora and Drača, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines",
pages = "83",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5284"
}

Komazec, T., Drača, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284

Komazec T, Drača D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .

Komazec, Teodora, Drača, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):83,
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .