TY  - CONF
AU  - Stanisavljević, Isidora
AU  - Pavlović, Slađana
AU  - Simović Marković, Bojana
AU  - Ćorović, Irfan
AU  - Krajnović, Tamara
AU  - Mijatović, Sanja
AU  - Jovanović, Ivan
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6993
AB  - Karcinom dojke je najčešći maligni tumor kod žena i obično je udružen sa ranim metastazama što predstavlja značajan zdravstveni problem. Imunski odgovor protiv karcinoma zasniva se na efektorskim dejstvima ćelija imunskog sistema, među kojima su najznačajnije NK ćelije i CD8+ T limfocite. Semaglutid je antidijabetik koji pripada grupi inkretinskih mimetika. Svoje efekte ostvaruje agonističkim dejstvom na receptore za peptid-sličan glukagonu 1 (Glucagon-like peptide-1, GLP-1). Antitumorski efekat agonista GLP-1 receptora ogleda se u inhibiciji rasta, proliferacije, migracije i invazivnosti tumorskih ćelija. Cilj ove studije je ispitati antitumorski efekat semaglutida u 4T1 eksperimentalnom modelu mišijeg karcinoma dojke. Nakon indukcije karcinoma dojke, BALB/c miševi su tretirani semaglutidom intraperitonealno. Primena semaglutida značajno je odložila pojavu palpabilnog tumora i usporila rast tumora. Istovremeno, antidijabetik nije pokazao direktno antitumorsko dejstvo u in vitro eksperimentima. Rezultati istraživanja ukazuju da semaglutid funkcionalni fenotip CD3-CD49b+ NK ćelija tako što pojačava ekspresiju aktivacionih receptora CD69 i NKG2D, a smanjuje ekspresiju PD-1 inhibitornog receptora i IL-10. Takođe, semaglutid je povećao infiltraciju tumora CD3+CD49b- T limfocitima kao i ekspresiju aktivacionih markera CD69 i NKG2D i pojačao produkciju granzima. Istovremeno je smanjio ekspresiju PD-1 i IL-10 na CD3+CD49b- T limfocitima. Semagutid nije uticao na povećanje ukupnog broja tumor infiltrišućih dendritksih ćelija ali je statistički značajno povećao ekspresiju kostimulatora CD86. Ovi rezultati ističu da semaglutid ima potencijal kao terapijski agens za stimulaciju imunskog sistema protiv tumora.
AB  - Карцином дојке је најчешћи малигни тумор код жена и обично је удружен са раним метастазама што представља значајан здравствени проблем. Имунски одговор против карцинома заснива се на ефекторским дејствима ћелија имунског система, међу којима су најзначајније NK ћелије и CD8+ Т лимфоците. Семаглутид је антидијабетик који припада групи инкретинских миметика. Своје ефекте остварује агонистичким дејством на рецепторе за пептид-сличан глукагону 1 (Glucagon-like peptide-1, GLP-1). Антитуморски ефекат агониста GLP-1 рецептора огледа се у инхибицији раста, пролиферације, миграције и инвазивности туморских ћелија. Циљ ове студије је испитати антитуморски ефекат семаглутида у 4T1 експерименталном моделу мишијег карцинома дојке. Након индукције карцинома дојке, BALB/c мишеви су третирани семаглутидом интраперитонеално. Примена семаглутида значајно је одложила појаву палпабилног тумора и успорила раст тумора. Истовремено, антидијабетик није показао директно антитуморско дејство у in vitro експериментима. Резултати истраживања указују да семаглутид функционални фенотип CD3-CD49b+ NK ћелија тако што појачава експресију активационих рецептора CD69 и NKG2D, а смањује експресију PD-1 инхибиторног рецептора и IL-10. Такође, семаглутид је повећао инфилтрацију тумора CD3+CD49b- Т лимфоцитима као и експресију активационих маркера CD69 и NKG2D и појачао продукцију гранзима. Истовремено је смањио експресију PD-1 и IL-10 на CD3+CD49b- Т лимфоцитима. Семагутид није утицао на повећање укупног броја тумор инфилтришућих дендритксих ћелија али је статистички значајно повећао експресију костимулатора CD86. Ови резултати истичу да семаглутид има потенцијал као терапијски агенс за стимулацију имунског система против тумора.
PB  - Beograd, Srbija: Srpska akademija nauka i umetnosti
C3  - Naučni skup Svetski dan imunologije 2024; 2024 Apr 25; Belgrade, Serbia
T1  - Semaglutid kao potentan aktivator antitumorskog imunskog odgovora u karcinomu dojke
T1  - Семаглутид као потентан активатор антитуморског имунског одговора у карциному дојке
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6993
ER  - 

@conference{
author = "Stanisavljević, Isidora and Pavlović, Slađana and Simović Marković, Bojana and Ćorović, Irfan and Krajnović, Tamara and Mijatović, Sanja and Jovanović, Ivan",
year = "2024",
abstract = "Karcinom dojke je najčešći maligni tumor kod žena i obično je udružen sa ranim metastazama što predstavlja značajan zdravstveni problem. Imunski odgovor protiv karcinoma zasniva se na efektorskim dejstvima ćelija imunskog sistema, među kojima su najznačajnije NK ćelije i CD8+ T limfocite. Semaglutid je antidijabetik koji pripada grupi inkretinskih mimetika. Svoje efekte ostvaruje agonističkim dejstvom na receptore za peptid-sličan glukagonu 1 (Glucagon-like peptide-1, GLP-1). Antitumorski efekat agonista GLP-1 receptora ogleda se u inhibiciji rasta, proliferacije, migracije i invazivnosti tumorskih ćelija. Cilj ove studije je ispitati antitumorski efekat semaglutida u 4T1 eksperimentalnom modelu mišijeg karcinoma dojke. Nakon indukcije karcinoma dojke, BALB/c miševi su tretirani semaglutidom intraperitonealno. Primena semaglutida značajno je odložila pojavu palpabilnog tumora i usporila rast tumora. Istovremeno, antidijabetik nije pokazao direktno antitumorsko dejstvo u in vitro eksperimentima. Rezultati istraživanja ukazuju da semaglutid funkcionalni fenotip CD3-CD49b+ NK ćelija tako što pojačava ekspresiju aktivacionih receptora CD69 i NKG2D, a smanjuje ekspresiju PD-1 inhibitornog receptora i IL-10. Takođe, semaglutid je povećao infiltraciju tumora CD3+CD49b- T limfocitima kao i ekspresiju aktivacionih markera CD69 i NKG2D i pojačao produkciju granzima. Istovremeno je smanjio ekspresiju PD-1 i IL-10 na CD3+CD49b- T limfocitima. Semagutid nije uticao na povećanje ukupnog broja tumor infiltrišućih dendritksih ćelija ali je statistički značajno povećao ekspresiju kostimulatora CD86. Ovi rezultati ističu da semaglutid ima potencijal kao terapijski agens za stimulaciju imunskog sistema protiv tumora., Карцином дојке је најчешћи малигни тумор код жена и обично је удружен са раним метастазама што представља значајан здравствени проблем. Имунски одговор против карцинома заснива се на ефекторским дејствима ћелија имунског система, међу којима су најзначајније NK ћелије и CD8+ Т лимфоците. Семаглутид је антидијабетик који припада групи инкретинских миметика. Своје ефекте остварује агонистичким дејством на рецепторе за пептид-сличан глукагону 1 (Glucagon-like peptide-1, GLP-1). Антитуморски ефекат агониста GLP-1 рецептора огледа се у инхибицији раста, пролиферације, миграције и инвазивности туморских ћелија. Циљ ове студије је испитати антитуморски ефекат семаглутида у 4T1 експерименталном моделу мишијег карцинома дојке. Након индукције карцинома дојке, BALB/c мишеви су третирани семаглутидом интраперитонеално. Примена семаглутида значајно је одложила појаву палпабилног тумора и успорила раст тумора. Истовремено, антидијабетик није показао директно антитуморско дејство у in vitro експериментима. Резултати истраживања указују да семаглутид функционални фенотип CD3-CD49b+ NK ћелија тако што појачава експресију активационих рецептора CD69 и NKG2D, а смањује експресију PD-1 инхибиторног рецептора и IL-10. Такође, семаглутид је повећао инфилтрацију тумора CD3+CD49b- Т лимфоцитима као и експресију активационих маркера CD69 и NKG2D и појачао продукцију гранзима. Истовремено је смањио експресију PD-1 и IL-10 на CD3+CD49b- Т лимфоцитима. Семагутид није утицао на повећање укупног броја тумор инфилтришућих дендритксих ћелија али је статистички значајно повећао експресију костимулатора CD86. Ови резултати истичу да семаглутид има потенцијал као терапијски агенс за стимулацију имунског система против тумора.",
publisher = "Beograd, Srbija: Srpska akademija nauka i umetnosti",
journal = "Naučni skup Svetski dan imunologije 2024; 2024 Apr 25; Belgrade, Serbia",
title = "Semaglutid kao potentan aktivator antitumorskog imunskog odgovora u karcinomu dojke, Семаглутид као потентан активатор антитуморског имунског одговора у карциному дојке",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6993"
}

Stanisavljević, I., Pavlović, S., Simović Marković, B., Ćorović, I., Krajnović, T., Mijatović, S.,& Jovanović, I.. (2024). Semaglutid kao potentan aktivator antitumorskog imunskog odgovora u karcinomu dojke. in Naučni skup Svetski dan imunologije 2024; 2024 Apr 25; Belgrade, Serbia
Beograd, Srbija: Srpska akademija nauka i umetnosti., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_6993

Stanisavljević I, Pavlović S, Simović Marković B, Ćorović I, Krajnović T, Mijatović S, Jovanović I. Semaglutid kao potentan aktivator antitumorskog imunskog odgovora u karcinomu dojke. in Naučni skup Svetski dan imunologije 2024; 2024 Apr 25; Belgrade, Serbia. 2024;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_6993 .

Stanisavljević, Isidora, Pavlović, Slađana, Simović Marković, Bojana, Ćorović, Irfan, Krajnović, Tamara, Mijatović, Sanja, Jovanović, Ivan, "Semaglutid kao potentan aktivator antitumorskog imunskog odgovora u karcinomu dojke" in Naučni skup Svetski dan imunologije 2024; 2024 Apr 25; Belgrade, Serbia (2024):17,
https://hdl.handle.net/21.15107/rcub_ibiss_6993 .

TY  - JOUR
AU  - Mihajlović, Ekatarina
AU  - Biancalana, Lorenzo
AU  - Jelača, Sanja
AU  - Chiaverini, Lorenzo
AU  - Dojčinović, Biljana
AU  - Dunđerović, Duško
AU  - Zacchini, Stefano
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Marchetti, Fabio
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6701
AB  - FETPY, an organo-diiron(I) complex, showed strong cytotoxicity across a panel of human and mouse cancer cell lines, combined with an outstanding selectivity compared to nonmalignant cells. Enhanced iron uptake in aggressive, low-differentiated cell lines, caused membrane lipid peroxidation, which resulted in ferroptosis in human ovarian cancer cells. FETPY induced significant morphological changes in murine B16–F1 and B16–F10 melanoma cells, leading to senescence and/or trans-differentiation into Schwann-like cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in low- and high-grade syngeneic melanoma models when administered in a therapeutic regimen. FETPY is featured by satisfactory water solubility (millimolar range), an amphiphilic character (Log Pow = −0.17), and excellent stability in a biological medium (DMEM). These important requisites for drug development are rarely met in iron complexes investigated so far as possible anticancer agents. Overall, FETPY holds promise as a safe and potent targeted antitumor agent.
PB  - American Chemical Society
T2  - Journal of Medicinal Chemistry
T1  - FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo
IS  - 9
VL  - 67
DO  - 10.1021/acs.jmedchem.4c00377
SP  - 7553
EP  - 7568
ER  - 

@article{
author = "Mihajlović, Ekatarina and Biancalana, Lorenzo and Jelača, Sanja and Chiaverini, Lorenzo and Dojčinović, Biljana and Dunđerović, Duško and Zacchini, Stefano and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Marchetti, Fabio",
year = "2024",
abstract = "FETPY, an organo-diiron(I) complex, showed strong cytotoxicity across a panel of human and mouse cancer cell lines, combined with an outstanding selectivity compared to nonmalignant cells. Enhanced iron uptake in aggressive, low-differentiated cell lines, caused membrane lipid peroxidation, which resulted in ferroptosis in human ovarian cancer cells. FETPY induced significant morphological changes in murine B16–F1 and B16–F10 melanoma cells, leading to senescence and/or trans-differentiation into Schwann-like cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in low- and high-grade syngeneic melanoma models when administered in a therapeutic regimen. FETPY is featured by satisfactory water solubility (millimolar range), an amphiphilic character (Log Pow = −0.17), and excellent stability in a biological medium (DMEM). These important requisites for drug development are rarely met in iron complexes investigated so far as possible anticancer agents. Overall, FETPY holds promise as a safe and potent targeted antitumor agent.",
publisher = "American Chemical Society",
journal = "Journal of Medicinal Chemistry",
title = "FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo",
number = "9",
volume = "67",
doi = "10.1021/acs.jmedchem.4c00377",
pages = "7553-7568"
}

Mihajlović, E., Biancalana, L., Jelača, S., Chiaverini, L., Dojčinović, B., Dunđerović, D., Zacchini, S., Mijatović, S., Maksimović-Ivanić, D.,& Marchetti, F.. (2024). FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo. in Journal of Medicinal Chemistry
American Chemical Society., 67(9), 7553-7568.
https://doi.org/10.1021/acs.jmedchem.4c00377

Mihajlović E, Biancalana L, Jelača S, Chiaverini L, Dojčinović B, Dunđerović D, Zacchini S, Mijatović S, Maksimović-Ivanić D, Marchetti F. FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo. in Journal of Medicinal Chemistry. 2024;67(9):7553-7568.
doi:10.1021/acs.jmedchem.4c00377 .

Mihajlović, Ekatarina, Biancalana, Lorenzo, Jelača, Sanja, Chiaverini, Lorenzo, Dojčinović, Biljana, Dunđerović, Duško, Zacchini, Stefano, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Marchetti, Fabio, "FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo" in Journal of Medicinal Chemistry, 67, no. 9 (2024):7553-7568,
https://doi.org/10.1021/acs.jmedchem.4c00377 . .

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  - 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  - Kazimir, Aleksandr
AU  - Götze, Tom
AU  - Murganić, Blagoje
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6853
AB  - Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.
PB  - The Royal Society of Chemistry
T2  - RSC Medicinal Chemistry
T1  - Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer
IS  - 6
VL  - 15
DO  - 10.1039/D4MD00051J
SP  - 1921
EP  - 1928
ER  - 

@article{
author = "Kazimir, Aleksandr and Götze, Tom and Murganić, Blagoje and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2024",
abstract = "Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.",
publisher = "The Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer",
number = "6",
volume = "15",
doi = "10.1039/D4MD00051J",
pages = "1921-1928"
}

Kazimir, A., Götze, T., Murganić, B., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2024). Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer. in RSC Medicinal Chemistry
The Royal Society of Chemistry., 15(6), 1921-1928.
https://doi.org/10.1039/D4MD00051J

Kazimir A, Götze T, Murganić B, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer. in RSC Medicinal Chemistry. 2024;15(6):1921-1928.
doi:10.1039/D4MD00051J .

Kazimir, Aleksandr, Götze, Tom, Murganić, Blagoje, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer" in RSC Medicinal Chemistry, 15, no. 6 (2024):1921-1928,
https://doi.org/10.1039/D4MD00051J . .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Jovanović, Ivan
AU  - Bovan, Dijana
AU  - Pavlović, Slađana
AU  - Gajović, Nevena
AU  - Dunđerović, Duško
AU  - Dajić-Stevanović, Zora
AU  - Acović, Aleksandar
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6854
AB  - Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady’s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.
PB  - Basel: MDPI
T2  - Diseases
T1  - Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study
IS  - 6
VL  - 12
DO  - 10.3390/diseases12060125
SP  - 125
ER  - 

@article{
author = "Jelača, Sanja and Jovanović, Ivan and Bovan, Dijana and Pavlović, Slađana and Gajović, Nevena and Dunđerović, Duško and Dajić-Stevanović, Zora and Acović, Aleksandar and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady’s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.",
publisher = "Basel: MDPI",
journal = "Diseases",
title = "Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study",
number = "6",
volume = "12",
doi = "10.3390/diseases12060125",
pages = "125"
}

Jelača, S., Jovanović, I., Bovan, D., Pavlović, S., Gajović, N., Dunđerović, D., Dajić-Stevanović, Z., Acović, A., Mijatović, S.,& Maksimović-Ivanić, D.. (2024). Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study. in Diseases
Basel: MDPI., 12(6), 125.
https://doi.org/10.3390/diseases12060125

Jelača S, Jovanović I, Bovan D, Pavlović S, Gajović N, Dunđerović D, Dajić-Stevanović Z, Acović A, Mijatović S, Maksimović-Ivanić D. Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study. in Diseases. 2024;12(6):125.
doi:10.3390/diseases12060125 .

Jelača, Sanja, Jovanović, Ivan, Bovan, Dijana, Pavlović, Slađana, Gajović, Nevena, Dunđerović, Duško, Dajić-Stevanović, Zora, Acović, Aleksandar, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study" in Diseases, 12, no. 6 (2024):125,
https://doi.org/10.3390/diseases12060125 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Götze, Tom
AU  - Lönnecke, Peter
AU  - Murganić, Blagoje
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6851
AB  - Triple-negative breast cancer (TNBC) poses challenges in therapy due to the absence of target expression such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal 
growth factor receptor 2 (HER2). Frequently, the treatment of TNBC involves the combination of several therapeutics. However, an enhanced therapeutic effect can be also achieved within a single molecule. The efficacy of raloxifene can be improved by designing a raloxifene-based hybrid drug bearing a 2,2’-bipyridine moiety (2). Integration of platinum(II), palladium(II), and nickel(II) complexes into 
this structure dramatically changed the cytotoxicity. The platinum(II) dichloride complex 3 did not demonstrate any activity, while palladium(II) and nickel(II) dichloride complexes 4 and 5 exhibited 
various cytotoxic behavior towards different types of hormone-receptor positive (HR+) cancer and TNBC cell lines. The replacement of the two chlorido ligands in 3‒5 with a dicarbollide (carborate) ion
[C2B9H11]2- resulted in reduced activity of compounds 6, 7, and 8. However, the palladacarborane complex 7 demonstrated higher selectivity towards TNBC. Furthermore, the mechanism of action was 
shifted from cytotoxic to explicitly cytostatic with detectable proliferation arrest and accelerated aging, characterized by senescence-associated phenotype of TNBC cells. This study provides valuable insights into the development of hybrid therapeutics against TNBC.
PB  - John Wiley and Sons
T2  - ChemMedChem
T1  - Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer
DO  - 10.1002/cmdc.202400006
SP  - e202400006
ER  - 

@article{
author = "Kazimir, Aleksandr and Götze, Tom and Lönnecke, Peter and Murganić, Blagoje and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2024",
abstract = "Triple-negative breast cancer (TNBC) poses challenges in therapy due to the absence of target expression such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal 
growth factor receptor 2 (HER2). Frequently, the treatment of TNBC involves the combination of several therapeutics. However, an enhanced therapeutic effect can be also achieved within a single molecule. The efficacy of raloxifene can be improved by designing a raloxifene-based hybrid drug bearing a 2,2’-bipyridine moiety (2). Integration of platinum(II), palladium(II), and nickel(II) complexes into 
this structure dramatically changed the cytotoxicity. The platinum(II) dichloride complex 3 did not demonstrate any activity, while palladium(II) and nickel(II) dichloride complexes 4 and 5 exhibited 
various cytotoxic behavior towards different types of hormone-receptor positive (HR+) cancer and TNBC cell lines. The replacement of the two chlorido ligands in 3‒5 with a dicarbollide (carborate) ion
[C2B9H11]2- resulted in reduced activity of compounds 6, 7, and 8. However, the palladacarborane complex 7 demonstrated higher selectivity towards TNBC. Furthermore, the mechanism of action was 
shifted from cytotoxic to explicitly cytostatic with detectable proliferation arrest and accelerated aging, characterized by senescence-associated phenotype of TNBC cells. This study provides valuable insights into the development of hybrid therapeutics against TNBC.",
publisher = "John Wiley and Sons",
journal = "ChemMedChem",
title = "Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer",
doi = "10.1002/cmdc.202400006",
pages = "e202400006"
}

Kazimir, A., Götze, T., Lönnecke, P., Murganić, B., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2024). Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer. in ChemMedChem
John Wiley and Sons., e202400006.
https://doi.org/10.1002/cmdc.202400006

Kazimir A, Götze T, Lönnecke P, Murganić B, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer. in ChemMedChem. 2024;:e202400006.
doi:10.1002/cmdc.202400006 .

Kazimir, Aleksandr, Götze, Tom, Lönnecke, Peter, Murganić, Blagoje, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer" in ChemMedChem (2024):e202400006,
https://doi.org/10.1002/cmdc.202400006 . .

TY  - JOUR
AU  - Kasalović, Marijana P.
AU  - Jelača, Sanja
AU  - Milanović, Žiko
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Lađarević, Jelena
AU  - Božić, Bojan
AU  - Marković, Zoran
AU  - Dunđerović, Duško
AU  - Rüffer, Tobias
AU  - Kretschmer, Robert
AU  - Kaluđerović, Goran N.
AU  - Pantelić, Nebojša Đ.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6821
AB  - Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1− = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2− = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3− = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.
PB  - Cambridge: The Royal Society of Chemistry
T2  - Dalton Transactions
T1  - Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation
IS  - 19
VL  - 53
DO  - 10.1039/D4DT00182F
SP  - 8298
EP  - 8314
ER  - 

@article{
author = "Kasalović, Marijana P. and Jelača, Sanja and Milanović, Žiko and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Lađarević, Jelena and Božić, Bojan and Marković, Zoran and Dunđerović, Duško and Rüffer, Tobias and Kretschmer, Robert and Kaluđerović, Goran N. and Pantelić, Nebojša Đ.",
year = "2024",
abstract = "Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1− = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2− = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3− = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.",
publisher = "Cambridge: The Royal Society of Chemistry",
journal = "Dalton Transactions",
title = "Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation",
number = "19",
volume = "53",
doi = "10.1039/D4DT00182F",
pages = "8298-8314"
}

Kasalović, M. P., Jelača, S., Milanović, Ž., Maksimović-Ivanić, D., Mijatović, S., Lađarević, J., Božić, B., Marković, Z., Dunđerović, D., Rüffer, T., Kretschmer, R., Kaluđerović, G. N.,& Pantelić, N. Đ.. (2024). Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation. in Dalton Transactions
Cambridge: The Royal Society of Chemistry., 53(19), 8298-8314.
https://doi.org/10.1039/D4DT00182F

Kasalović MP, Jelača S, Milanović Ž, Maksimović-Ivanić D, Mijatović S, Lađarević J, Božić B, Marković Z, Dunđerović D, Rüffer T, Kretschmer R, Kaluđerović GN, Pantelić NĐ. Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation. in Dalton Transactions. 2024;53(19):8298-8314.
doi:10.1039/D4DT00182F .

Kasalović, Marijana P., Jelača, Sanja, Milanović, Žiko, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Lađarević, Jelena, Božić, Bojan, Marković, Zoran, Dunđerović, Duško, Rüffer, Tobias, Kretschmer, Robert, Kaluđerović, Goran N., Pantelić, Nebojša Đ., "Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation" in Dalton Transactions, 53, no. 19 (2024):8298-8314,
https://doi.org/10.1039/D4DT00182F . .

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  - Braun, Sebastian
AU  - Jelača, Sanja
AU  - Laube, Marcus
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/123456789/5823
AB  - Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.
PB  - Basel: MDPI
T2  - Molecules
T1  - Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs
IS  - 11
VL  - 28
DO  - 10.3390/molecules28114547
SP  - 4547
ER  - 

@article{
author = "Braun, Sebastian and Jelača, Sanja and Laube, Marcus 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 = "Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs",
number = "11",
volume = "28",
doi = "10.3390/molecules28114547",
pages = "4547"
}

Braun, S., Jelača, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules
Basel: MDPI., 28(11), 4547.
https://doi.org/10.3390/molecules28114547

Braun S, Jelača S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules. 2023;28(11):4547.
doi:10.3390/molecules28114547 .

Braun, Sebastian, Jelača, Sanja, Laube, Marcus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs" in Molecules, 28, no. 11 (2023):4547,
https://doi.org/10.3390/molecules28114547 . .

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  - 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/123456789/5469
AB  - The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes
IS  - 2
VL  - 15
DO  - 10.3390/pharmaceutics15020682
SP  - 682
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 = "The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes",
number = "2",
volume = "15",
doi = "10.3390/pharmaceutics15020682",
pages = "682"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics
Basel: MDPI., 15(2), 682.
https://doi.org/10.3390/pharmaceutics15020682

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics. 2023;15(2):682.
doi:10.3390/pharmaceutics15020682 .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes" in Pharmaceutics, 15, no. 2 (2023):682,
https://doi.org/10.3390/pharmaceutics15020682 . .

TY  - JOUR
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Bovan, Dijana
AU  - Jelača, Sanja
AU  - Jović, Zorana
AU  - Purić, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5470
AB  - In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo
IS  - 3
VL  - 13
DO  - 10.3390/nano13030372
SP  - 372
ER  - 

@article{
author = "Markelić, Milica and Mojić, Marija and Bovan, Dijana and Jelača, Sanja and Jović, Zorana and Purić, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo",
number = "3",
volume = "13",
doi = "10.3390/nano13030372",
pages = "372"
}

Markelić, M., Mojić, M., Bovan, D., Jelača, S., Jović, Z., Purić, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials
Basel: MDPI., 13(3), 372.
https://doi.org/10.3390/nano13030372

Markelić M, Mojić M, Bovan D, Jelača S, Jović Z, Purić M, Koruga D, Mijatović S, Maksimović-Ivanić D. Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials. 2023;13(3):372.
doi:10.3390/nano13030372 .

Markelić, Milica, Mojić, Marija, Bovan, Dijana, Jelača, Sanja, Jović, Zorana, Purić, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo" in Nanomaterials, 13, no. 3 (2023):372,
https://doi.org/10.3390/nano13030372 . .

TY  - JOUR
AU  - Stockmann, Philipp
AU  - Kuhnert, Lydia
AU  - Leinung, Wencke
AU  - Lakoma, Cathleen
AU  - Scholz, Birte
AU  - Paskaš, Svetlana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Honscha, Walther
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - https://www.mdpi.com/1999-4923/15/1/241
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9866861
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5434
AB  - The ineffectiveness and failing of chemotherapeutic treatments are often associated with multidrug resistance (MDR). MDR is primarily linked to the overexpression of ATP-binding cassette (ABC) transporter proteins in cancer cells. ABCG2 (ATP-binding cassette subfamily G member 2, also known as the breast cancer resistance protein (BCRP)) mediates MDR by an increased drug efflux from the cancer cells. Therefore, the inhibition of ABCG2 activity during chemotherapy ought to improve the efficacy of the administered anti-cancer agents by reversing MDR or by enhancing the agents' pharmacokinetic properties. Significant efforts have been made to develop novel, powerful, selective, and non-toxic inhibitors of BCRP. However, thus far the clinical relevance of BCRP-selective MDR-reversal has been unsuccessful, due to either adverse drug reactions or significant toxicities in vivo. We here report a facile access towards carboranyl quinazoline-based inhibitors of ABCG2. We determined the influence of different methoxy-substitution patterns on the 2-phenylquinazoline scaffold in combination with the beneficial properties of an incorporated inorganic carborane moiety. A series of eight compounds was synthesized and their inhibitory effect on the ABCG2-mediated Hoechst transport was evaluated. Molecular docking studies were performed to better understand the structure-protein interactions of the novel inhibitors, exhibiting putative binding modes within the inner binding site. Further, the most potent, non-toxic compounds were investigated for their potential to reverse ABCG2-mediated mitoxantrone (MXN) resistance. Of these five evaluated compounds, N-(closo-1,7-dicarbadodecaboran(12)-9-yl)-6,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-quinazolin-4-amine (DMQCd) exhibited the strongest inhibitory effect towards ABCG2 in the lower nanomolar ranges. Additionally, DMQCd was able to reverse BCRP-mediated MDR, making it a promising candidate for further research on hybrid inorganic-organic compounds.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors
IS  - 1
VL  - 15
DO  - 10.3390/pharmaceutics15010241
SP  - 241
ER  - 

@article{
author = "Stockmann, Philipp and Kuhnert, Lydia and Leinung, Wencke and Lakoma, Cathleen and Scholz, Birte and Paskaš, Svetlana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Honscha, Walther and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The ineffectiveness and failing of chemotherapeutic treatments are often associated with multidrug resistance (MDR). MDR is primarily linked to the overexpression of ATP-binding cassette (ABC) transporter proteins in cancer cells. ABCG2 (ATP-binding cassette subfamily G member 2, also known as the breast cancer resistance protein (BCRP)) mediates MDR by an increased drug efflux from the cancer cells. Therefore, the inhibition of ABCG2 activity during chemotherapy ought to improve the efficacy of the administered anti-cancer agents by reversing MDR or by enhancing the agents' pharmacokinetic properties. Significant efforts have been made to develop novel, powerful, selective, and non-toxic inhibitors of BCRP. However, thus far the clinical relevance of BCRP-selective MDR-reversal has been unsuccessful, due to either adverse drug reactions or significant toxicities in vivo. We here report a facile access towards carboranyl quinazoline-based inhibitors of ABCG2. We determined the influence of different methoxy-substitution patterns on the 2-phenylquinazoline scaffold in combination with the beneficial properties of an incorporated inorganic carborane moiety. A series of eight compounds was synthesized and their inhibitory effect on the ABCG2-mediated Hoechst transport was evaluated. Molecular docking studies were performed to better understand the structure-protein interactions of the novel inhibitors, exhibiting putative binding modes within the inner binding site. Further, the most potent, non-toxic compounds were investigated for their potential to reverse ABCG2-mediated mitoxantrone (MXN) resistance. Of these five evaluated compounds, N-(closo-1,7-dicarbadodecaboran(12)-9-yl)-6,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-quinazolin-4-amine (DMQCd) exhibited the strongest inhibitory effect towards ABCG2 in the lower nanomolar ranges. Additionally, DMQCd was able to reverse BCRP-mediated MDR, making it a promising candidate for further research on hybrid inorganic-organic compounds.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors",
number = "1",
volume = "15",
doi = "10.3390/pharmaceutics15010241",
pages = "241"
}

Stockmann, P., Kuhnert, L., Leinung, W., Lakoma, C., Scholz, B., Paskaš, S., Mijatović, S., Maksimović-Ivanić, D., Honscha, W.,& Hey-Hawkins, E.. (2023). The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors. in Pharmaceutics
Basel: MDPI., 15(1), 241.
https://doi.org/10.3390/pharmaceutics15010241

Stockmann P, Kuhnert L, Leinung W, Lakoma C, Scholz B, Paskaš S, Mijatović S, Maksimović-Ivanić D, Honscha W, Hey-Hawkins E. The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors. in Pharmaceutics. 2023;15(1):241.
doi:10.3390/pharmaceutics15010241 .

Stockmann, Philipp, Kuhnert, Lydia, Leinung, Wencke, Lakoma, Cathleen, Scholz, Birte, Paskaš, Svetlana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Honscha, Walther, Hey-Hawkins, Evamarie, "The More the Better-Investigation of Polymethoxylated N-Carboranyl Quinazolines as Novel Hybrid Breast Cancer Resistance Protein Inhibitors" in Pharmaceutics, 15, no. 1 (2023):241,
https://doi.org/10.3390/pharmaceutics15010241 . .

TY  - JOUR
AU  - Useini, Liridona
AU  - Mojić, Marija
AU  - Laube, Markus
AU  - Lönnecke, Peter
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Pietzsch, Jens
AU  - Hey‐Hawkins, Evamarie
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202200583
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5432
AB  - Fenoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX-1 the “house-keeping” enzyme and COX-2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off-target effects have also been reported. The steric modifications of the drugs could afford the desired COX-2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba-closo-dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl-based compounds.
PB  - John Wiley and Sons Ltd
T2  - ChemMedChem
T1  - Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity
IS  - 5
VL  - 18
DO  - 10.1002/cmdc.202200583
SP  - e202200583
ER  - 

@article{
author = "Useini, Liridona and Mojić, Marija and Laube, Markus and Lönnecke, Peter and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Pietzsch, Jens and Hey‐Hawkins, Evamarie",
year = "2023",
abstract = "Fenoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX-1 the “house-keeping” enzyme and COX-2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off-target effects have also been reported. The steric modifications of the drugs could afford the desired COX-2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba-closo-dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl-based compounds.",
publisher = "John Wiley and Sons Ltd",
journal = "ChemMedChem",
title = "Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity",
number = "5",
volume = "18",
doi = "10.1002/cmdc.202200583",
pages = "e202200583"
}

Useini, L., Mojić, M., Laube, M., Lönnecke, P., Mijatović, S., Maksimović-Ivanić, D., Pietzsch, J.,& Hey‐Hawkins, E.. (2023). Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity. in ChemMedChem
John Wiley and Sons Ltd., 18(5), e202200583.
https://doi.org/10.1002/cmdc.202200583

Useini L, Mojić M, Laube M, Lönnecke P, Mijatović S, Maksimović-Ivanić D, Pietzsch J, Hey‐Hawkins E. Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity. in ChemMedChem. 2023;18(5):e202200583.
doi:10.1002/cmdc.202200583 .

Useini, Liridona, Mojić, Marija, Laube, Markus, Lönnecke, Peter, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Pietzsch, Jens, Hey‐Hawkins, Evamarie, "Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity" in ChemMedChem, 18, no. 5 (2023):e202200583,
https://doi.org/10.1002/cmdc.202200583 . .

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  - https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200252
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5384
AB  - The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556 are presented. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.
T2  - Advanced Therapeutics
T1  - In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors
DO  - 10.1002/adtp.202200252
SP  - 2200252
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 selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556 are presented. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.",
journal = "Advanced Therapeutics",
title = "In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors",
doi = "10.1002/adtp.202200252",
pages = "2200252"
}

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). In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors. in Advanced Therapeutics, 2200252.
https://doi.org/10.1002/adtp.202200252

Braun S, Paskaš S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey‐Hawkins E. In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors. in Advanced Therapeutics. 2023;:2200252.
doi:10.1002/adtp.202200252 .

Braun, Sebastian, Paskaš, Svetlana, Laube, Markus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey‐Hawkins, Evamarie, "In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors" in Advanced Therapeutics (2023):2200252,
https://doi.org/10.1002/adtp.202200252 . .

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  - 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  - 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  - 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  - 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  - 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 . .