TY  - JOUR
AU  - Alov, Petko
AU  - Al Sharif, Merilin
AU  - Aluani, Denitsa
AU  - Chegaev, Konstantin
AU  - Dinić, Jelena
AU  - Divac Rankov, Aleksandra
AU  - Fernandes, Miguel X.
AU  - Fusi, Fabio
AU  - Garcia-Sosa, Alfonso T.
AU  - Juvonen, Risto
AU  - Kondeva-Burdina, Magdalena
AU  - Padron, Jose M.
AU  - Pajeva, Ilza
AU  - Pencheva, Tania
AU  - Puerta, Adrian
AU  - Raunio, Hannu
AU  - Riganti, Chiara
AU  - Tsakovska, Ivanka
AU  - Tzankova, Virginia
AU  - Yordanov, Yordan
AU  - Saponara, Simona
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1555
AB  - Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary in silico, in vitro, and in vivo approach. Doxorubicin was used as the reference compound. The in silico profiling suggested that Sdox possesses higher lipophilicity and lower solubility compared to doxorubicin, and the off-targets prediction revealed relevant differences between Dox and Sdox towards several cancer targets, suggesting different toxicological profiles. In vitro data showed that Sdox is a substrate with lower affinity for P-glycoprotein, less hepatotoxic, and causes less oxidative damage than doxorubicin. Both anthracyclines inhibited CYP3A4, but not hERG currents. Unlike doxorubicin, the percentage of zebrafish live embryos at 72 hpf was not affected by Sdox treatment. In conclusion, these findings demonstrate that Sdox displays a more favorable drug-like ADME/toxicity profile than doxorubicin, different selectivity towards cancer targets, along with a greater preclinical efficacy in resistant tumors. Therefore, Sdox represents a prototype of innovative anthracyclines, worthy of further investigations in clinical settings.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Pharmacology
T1  - A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors
VL  - 13
DO  - 10.3389/fphar.2022.831791
ER  - 

@article{
author = "Alov, Petko and Al Sharif, Merilin and Aluani, Denitsa and Chegaev, Konstantin and Dinić, Jelena and Divac Rankov, Aleksandra and Fernandes, Miguel X. and Fusi, Fabio and Garcia-Sosa, Alfonso T. and Juvonen, Risto and Kondeva-Burdina, Magdalena and Padron, Jose M. and Pajeva, Ilza and Pencheva, Tania and Puerta, Adrian and Raunio, Hannu and Riganti, Chiara and Tsakovska, Ivanka and Tzankova, Virginia and Yordanov, Yordan and Saponara, Simona",
year = "2022",
abstract = "Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary in silico, in vitro, and in vivo approach. Doxorubicin was used as the reference compound. The in silico profiling suggested that Sdox possesses higher lipophilicity and lower solubility compared to doxorubicin, and the off-targets prediction revealed relevant differences between Dox and Sdox towards several cancer targets, suggesting different toxicological profiles. In vitro data showed that Sdox is a substrate with lower affinity for P-glycoprotein, less hepatotoxic, and causes less oxidative damage than doxorubicin. Both anthracyclines inhibited CYP3A4, but not hERG currents. Unlike doxorubicin, the percentage of zebrafish live embryos at 72 hpf was not affected by Sdox treatment. In conclusion, these findings demonstrate that Sdox displays a more favorable drug-like ADME/toxicity profile than doxorubicin, different selectivity towards cancer targets, along with a greater preclinical efficacy in resistant tumors. Therefore, Sdox represents a prototype of innovative anthracyclines, worthy of further investigations in clinical settings.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Pharmacology",
title = "A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors",
volume = "13",
doi = "10.3389/fphar.2022.831791"
}

Alov, P., Al Sharif, M., Aluani, D., Chegaev, K., Dinić, J., Divac Rankov, A., Fernandes, M. X., Fusi, F., Garcia-Sosa, A. T., Juvonen, R., Kondeva-Burdina, M., Padron, J. M., Pajeva, I., Pencheva, T., Puerta, A., Raunio, H., Riganti, C., Tsakovska, I., Tzankova, V., Yordanov, Y.,& Saponara, S.. (2022). A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors. in Frontiers in Pharmacology
Frontiers Media Sa, Lausanne., 13.
https://doi.org/10.3389/fphar.2022.831791

Alov P, Al Sharif M, Aluani D, Chegaev K, Dinić J, Divac Rankov A, Fernandes MX, Fusi F, Garcia-Sosa AT, Juvonen R, Kondeva-Burdina M, Padron JM, Pajeva I, Pencheva T, Puerta A, Raunio H, Riganti C, Tsakovska I, Tzankova V, Yordanov Y, Saponara S. A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors. in Frontiers in Pharmacology. 2022;13.
doi:10.3389/fphar.2022.831791 .

Alov, Petko, Al Sharif, Merilin, Aluani, Denitsa, Chegaev, Konstantin, Dinić, Jelena, Divac Rankov, Aleksandra, Fernandes, Miguel X., Fusi, Fabio, Garcia-Sosa, Alfonso T., Juvonen, Risto, Kondeva-Burdina, Magdalena, Padron, Jose M., Pajeva, Ilza, Pencheva, Tania, Puerta, Adrian, Raunio, Hannu, Riganti, Chiara, Tsakovska, Ivanka, Tzankova, Virginia, Yordanov, Yordan, Saponara, Simona, "A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors" in Frontiers in Pharmacology, 13 (2022),
https://doi.org/10.3389/fphar.2022.831791 . .

TY  - JOUR
AU  - Marković, Sanja B.
AU  - Maciejewska, Natalia
AU  - Olszewski, Mateusz
AU  - Visnjevac, Aleksandar
AU  - Puerta, Adrian
AU  - Padron, Jose M.
AU  - Novaković, Irena
AU  - Kojić, Snežana
AU  - Fernandes, Henrique S.
AU  - Ramotowska, Sandra
AU  - Chylewska, Agnieszka
AU  - Makowski, Mariusz
AU  - Todorović, Tamara R.
AU  - Filipović, Nenad R.
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1551
AB  - The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity of cadmium complexes showed that the complexation of various ligands resulted in complexes that showed better activities than approved drugs. In the present study, cadmium complexes with biologically potent thiazolyl/selenazoyl-hydrazone ligands have been prepared, and tested for their activity against different types of tumor cell models. The complexation of ligands with Cd(II) resulted in a synergistic effect. The antiproliferative activity study revealed that all complexes are more active compared to 5-fluorouracil and cisplatin. The mechanism of tumor cell growth inhibition reveal that selenium-based compounds induce cell death in T-47D (gland carci-noma) cells through apoptosis via caspase-3/7 activation. Additionally, their pro-apoptotic effect was stronger compared to etoposide and cisplatin. Nuclease activity, detected by gel electrophoresis, may be the possible mechanism of anticancer action of investigated complexes.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters
VL  - 238
DO  - 10.1016/j.ejmech.2022.114449
ER  - 

@article{
author = "Marković, Sanja B. and Maciejewska, Natalia and Olszewski, Mateusz and Visnjevac, Aleksandar and Puerta, Adrian and Padron, Jose M. and Novaković, Irena and Kojić, Snežana and Fernandes, Henrique S. and Ramotowska, Sandra and Chylewska, Agnieszka and Makowski, Mariusz and Todorović, Tamara R. and Filipović, Nenad R.",
year = "2022",
abstract = "The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity of cadmium complexes showed that the complexation of various ligands resulted in complexes that showed better activities than approved drugs. In the present study, cadmium complexes with biologically potent thiazolyl/selenazoyl-hydrazone ligands have been prepared, and tested for their activity against different types of tumor cell models. The complexation of ligands with Cd(II) resulted in a synergistic effect. The antiproliferative activity study revealed that all complexes are more active compared to 5-fluorouracil and cisplatin. The mechanism of tumor cell growth inhibition reveal that selenium-based compounds induce cell death in T-47D (gland carci-noma) cells through apoptosis via caspase-3/7 activation. Additionally, their pro-apoptotic effect was stronger compared to etoposide and cisplatin. Nuclease activity, detected by gel electrophoresis, may be the possible mechanism of anticancer action of investigated complexes.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters",
volume = "238",
doi = "10.1016/j.ejmech.2022.114449"
}

Marković, S. B., Maciejewska, N., Olszewski, M., Visnjevac, A., Puerta, A., Padron, J. M., Novaković, I., Kojić, S., Fernandes, H. S., Ramotowska, S., Chylewska, A., Makowski, M., Todorović, T. R.,& Filipović, N. R.. (2022). Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 238.
https://doi.org/10.1016/j.ejmech.2022.114449

Marković SB, Maciejewska N, Olszewski M, Visnjevac A, Puerta A, Padron JM, Novaković I, Kojić S, Fernandes HS, Ramotowska S, Chylewska A, Makowski M, Todorović TR, Filipović NR. Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters. in European Journal of Medicinal Chemistry. 2022;238.
doi:10.1016/j.ejmech.2022.114449 .

Marković, Sanja B., Maciejewska, Natalia, Olszewski, Mateusz, Visnjevac, Aleksandar, Puerta, Adrian, Padron, Jose M., Novaković, Irena, Kojić, Snežana, Fernandes, Henrique S., Ramotowska, Sandra, Chylewska, Agnieszka, Makowski, Mariusz, Todorović, Tamara R., Filipović, Nenad R., "Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters" in European Journal of Medicinal Chemistry, 238 (2022),
https://doi.org/10.1016/j.ejmech.2022.114449 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Rios-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević Grujičić, Nataša
AU  - Martin, Victor S.
AU  - Padron, Jose M.
AU  - Pesić, Milica
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1766
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in beta-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
PB  - Elsevier Science Bv, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
EP  - 168
SP  - 159
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Rios-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević Grujičić, Nataša and Martin, Victor S. and Padron, Jose M. and Pesić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in beta-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
pages = "168-159",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011"
}

Podolski-Renić, A., Banković, J., Dinić, J., Rios-Luci, C., Fernandes, M. X., Ortega, N., Kovačević Grujičić, N., Martin, V. S., Padron, J. M.,& Pesić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences
Elsevier Science Bv, Amsterdam., 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Rios-Luci C, Fernandes MX, Ortega N, Kovačević Grujičić N, Martin VS, Padron JM, Pesić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Rios-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević Grujičić, Nataša, Martin, Victor S., Padron, Jose M., Pesić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .