TY  - JOUR
AU  - Jovanović, Mirna
AU  - Zhukovsky, Daniil
AU  - Podolski-Renić, Ana
AU  - Domračeva, Ilona
AU  - Žalubovskis, Raivis
AU  - Senćanski, Milan V.
AU  - Glišić, Sanja
AU  - Sharoyko, Vladimir
AU  - Tennikova, Tatiana
AU  - Dar'in, Dmitry
AU  - Pešić, Milica
AU  - Krasavin, Mikhail
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8532
AB  - A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization. © 2019 Elsevier Masson SAS
T2  - European Journal of Medicinal Chemistry
T1  - Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy
VL  - 181
SP  - 111580
DO  - 10.1016/j.ejmech.2019.111580
ER  - 

@article{
author = "Jovanović, Mirna and Zhukovsky, Daniil and Podolski-Renić, Ana and Domračeva, Ilona and Žalubovskis, Raivis and Senćanski, Milan V. and Glišić, Sanja and Sharoyko, Vladimir and Tennikova, Tatiana and Dar'in, Dmitry and Pešić, Milica and Krasavin, Mikhail",
year = "2019",
abstract = "A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization. © 2019 Elsevier Masson SAS",
journal = "European Journal of Medicinal Chemistry",
title = "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy",
volume = "181",
pages = "111580",
doi = "10.1016/j.ejmech.2019.111580"
}

Jovanović, M., Zhukovsky, D., Podolski-Renić, A., Domračeva, I., Žalubovskis, R., Senćanski, M. V., Glišić, S., Sharoyko, V., Tennikova, T., Dar'in, D., Pešić, M.,& Krasavin, M.. (2019). Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy. in European Journal of Medicinal Chemistry, 181, 111580.
https://doi.org/10.1016/j.ejmech.2019.111580

Jovanović M, Zhukovsky D, Podolski-Renić A, Domračeva I, Žalubovskis R, Senćanski MV, Glišić S, Sharoyko V, Tennikova T, Dar'in D, Pešić M, Krasavin M. Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy. in European Journal of Medicinal Chemistry. 2019;181:111580.
doi:10.1016/j.ejmech.2019.111580 .

Jovanović, Mirna, Zhukovsky, Daniil, Podolski-Renić, Ana, Domračeva, Ilona, Žalubovskis, Raivis, Senćanski, Milan V., Glišić, Sanja, Sharoyko, Vladimir, Tennikova, Tatiana, Dar'in, Dmitry, Pešić, Milica, Krasavin, Mikhail, "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy" in European Journal of Medicinal Chemistry, 181 (2019):111580,
https://doi.org/10.1016/j.ejmech.2019.111580 . .

TY  - JOUR
AU  - Pešić, Milica
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Matović, Branko
AU  - Zmejkoski, Danica
AU  - Kojić, Vesna
AU  - Bogdanović, Gordana
AU  - Pavicevic, Aleksandra
AU  - Mojovic, Milos
AU  - Savić, Aleksandar
AU  - Milenković, Ivana
AU  - Kalauzi, Aleksandar
AU  - Radotić, Ksenija
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/519
AB  - Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
T2  - Chemico-Biological Interactions
T1  - Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity
VL  - 232
SP  - 85
EP  - 93
DO  - 10.1016/j.cbi.2015.03.013
ER  - 

@article{
author = "Pešić, Milica and Podolski-Renić, Ana and Stojković, Sonja and Matović, Branko and Zmejkoski, Danica and Kojić, Vesna and Bogdanović, Gordana and Pavicevic, Aleksandra and Mojovic, Milos and Savić, Aleksandar and Milenković, Ivana and Kalauzi, Aleksandar and Radotić, Ksenija",
year = "2015",
abstract = "Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved.",
journal = "Chemico-Biological Interactions",
title = "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity",
volume = "232",
pages = "85-93",
doi = "10.1016/j.cbi.2015.03.013"
}

Pešić, M., Podolski-Renić, A., Stojković, S., Matović, B., Zmejkoski, D., Kojić, V., Bogdanović, G., Pavicevic, A., Mojovic, M., Savić, A., Milenković, I., Kalauzi, A.,& Radotić, K.. (2015). Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions, 232, 85-93.
https://doi.org/10.1016/j.cbi.2015.03.013

Pešić M, Podolski-Renić A, Stojković S, Matović B, Zmejkoski D, Kojić V, Bogdanović G, Pavicevic A, Mojovic M, Savić A, Milenković I, Kalauzi A, Radotić K. Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions. 2015;232:85-93.
doi:10.1016/j.cbi.2015.03.013 .

Pešić, Milica, Podolski-Renić, Ana, Stojković, Sonja, Matović, Branko, Zmejkoski, Danica, Kojić, Vesna, Bogdanović, Gordana, Pavicevic, Aleksandra, Mojovic, Milos, Savić, Aleksandar, Milenković, Ivana, Kalauzi, Aleksandar, Radotić, Ksenija, "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity" in Chemico-Biological Interactions, 232 (2015):85-93,
https://doi.org/10.1016/j.cbi.2015.03.013 . .

TY  - JOUR
AU  - Ruždijić, Sabera
AU  - Milošević, Jovan
AU  - Popović, Nataša M.
AU  - Pešić, Milica
AU  - Stojilkovic, M
AU  - Kanazir, Selma
AU  - Todorović, Danijela V.
AU  - Ristić-Fira, Aleksandra
AU  - Krstić-Demonacos, Marija
AU  - Kanazir, Selma
AU  - Rakić, Ljubisav
PY  - 2001
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2423
AB  - Tiazofurin and 8-Cl-cAMP are novel antineoplastic agents that have been shown to be effective against various cancer cells in vitro and in vivo. Through specific mechanisms of action they modulate the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, apoptosis and downregulation of c-ras and c-myc gene expression. We examined the effects of 8-Cl-cAMP and tiazofurin, either separately or together, on apoptosis induction and c-fos and c-myc expression in melanoma cells. 8-Cl-cAMP and tiazofurin inhibited the growth of melanoma cells in a dose-responsive manner. Whether used separately or together, each agent induced apoptotic cell death. Apoptosis was accompanied by a marked inhibition of c-fos and c-mye gene expression. RT-PCR analysis showed that 8-Cl-cAMP, together with tiazofurin, promoted 61% and 75% decreases of c-myc and c-fos expression in melanoma cells respectively. These results clearly indicate that the combination of 8-Cl-cAMP and tiazofurin could provide a promising therapeutic approach for melanoma treatment.
T2  - Jugoslovenska Medicinska Biohemija
T1  - Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells
VL  - 20
IS  - 1
SP  - 9
EP  - 18
UR  - https://hdl.handle.net/21.15107/rcub_vinar_2423
ER  - 

@article{
author = "Ruždijić, Sabera and Milošević, Jovan and Popović, Nataša M. and Pešić, Milica and Stojilkovic, M and Kanazir, Selma and Todorović, Danijela V. and Ristić-Fira, Aleksandra and Krstić-Demonacos, Marija and Kanazir, Selma and Rakić, Ljubisav",
year = "2001",
abstract = "Tiazofurin and 8-Cl-cAMP are novel antineoplastic agents that have been shown to be effective against various cancer cells in vitro and in vivo. Through specific mechanisms of action they modulate the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, apoptosis and downregulation of c-ras and c-myc gene expression. We examined the effects of 8-Cl-cAMP and tiazofurin, either separately or together, on apoptosis induction and c-fos and c-myc expression in melanoma cells. 8-Cl-cAMP and tiazofurin inhibited the growth of melanoma cells in a dose-responsive manner. Whether used separately or together, each agent induced apoptotic cell death. Apoptosis was accompanied by a marked inhibition of c-fos and c-mye gene expression. RT-PCR analysis showed that 8-Cl-cAMP, together with tiazofurin, promoted 61% and 75% decreases of c-myc and c-fos expression in melanoma cells respectively. These results clearly indicate that the combination of 8-Cl-cAMP and tiazofurin could provide a promising therapeutic approach for melanoma treatment.",
journal = "Jugoslovenska Medicinska Biohemija",
title = "Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells",
volume = "20",
number = "1",
pages = "9-18",
url = "https://hdl.handle.net/21.15107/rcub_vinar_2423"
}

Ruždijić, S., Milošević, J., Popović, N. M., Pešić, M., Stojilkovic, M., Kanazir, S., Todorović, D. V., Ristić-Fira, A., Krstić-Demonacos, M., Kanazir, S.,& Rakić, L.. (2001). Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells. in Jugoslovenska Medicinska Biohemija, 20(1), 9-18.
https://hdl.handle.net/21.15107/rcub_vinar_2423

Ruždijić S, Milošević J, Popović NM, Pešić M, Stojilkovic M, Kanazir S, Todorović DV, Ristić-Fira A, Krstić-Demonacos M, Kanazir S, Rakić L. Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells. in Jugoslovenska Medicinska Biohemija. 2001;20(1):9-18.
https://hdl.handle.net/21.15107/rcub_vinar_2423 .

Ruždijić, Sabera, Milošević, Jovan, Popović, Nataša M., Pešić, Milica, Stojilkovic, M, Kanazir, Selma, Todorović, Danijela V., Ristić-Fira, Aleksandra, Krstić-Demonacos, Marija, Kanazir, Selma, Rakić, Ljubisav, "Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells" in Jugoslovenska Medicinska Biohemija, 20, no. 1 (2001):9-18,
https://hdl.handle.net/21.15107/rcub_vinar_2423 .