TY  - CONF
AU  - Damjanović, Ana
AU  - Vuković, Miodrag
AU  - Vukadinović, Dragana
AU  - Dobričić, Vladimir
AU  - Grahovac, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5450
AB  - Melanoma is one of the most aggressive malignancies, where the prognosis for metastatic patients remains extremely poor. Our group has shown that the antihypertensive drug telmisartan has antimelanoma potential1. Given that the antihypertensive effect is not favorable in cancer patients, the aim of this study was to design and test novel telmisartan derivatives without the angiotensin receptor 1 (AT1R) binding activity. New derivatives were designed by modification of the carboxylic group, in order to alter telmisartan geometry and its AT1R binding properties. Eight derivatives, from which the lack of AT1R antagonistic activity could be expected based on molecular docking, were synthetized and selected for in vitro testing. After the cytotoxicity test on human melanoma cell lines A375 and 518a2, three derivatives that were twice more potent than telmisartan itself were selected for further analysis. The new derivatives induced mitochondrial fragmentation, generation of the mitochondrial reactive oxygen species, and decrease of mitochondrial membrane potential in melanoma cells, the mechanism we previously shown for induction of apoptosis by telmisartan in melanoma cells. As the new derivatives showed more potent effect on melanoma cells than telmisartan these results lay a ground for further preclinical testing in melanoma.
PB  - Croatian Association for Cancer Research, Zagreb, Croatia
C3  - “HDIR-6: Targeting Cancer”, The 6th Meeting of the Croatian Association for Cancer Research with International Participation, November 10-12, 2022, Book of Abstracts
T1  - Antimelanoma Potential of New Telmisartan Analogues Without AT1 Receptor Activity
SP  - 20
EP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5450
ER  - 

@conference{
author = "Damjanović, Ana and Vuković, Miodrag and Vukadinović, Dragana and Dobričić, Vladimir and Grahovac, Jelena",
year = "2022",
abstract = "Melanoma is one of the most aggressive malignancies, where the prognosis for metastatic patients remains extremely poor. Our group has shown that the antihypertensive drug telmisartan has antimelanoma potential1. Given that the antihypertensive effect is not favorable in cancer patients, the aim of this study was to design and test novel telmisartan derivatives without the angiotensin receptor 1 (AT1R) binding activity. New derivatives were designed by modification of the carboxylic group, in order to alter telmisartan geometry and its AT1R binding properties. Eight derivatives, from which the lack of AT1R antagonistic activity could be expected based on molecular docking, were synthetized and selected for in vitro testing. After the cytotoxicity test on human melanoma cell lines A375 and 518a2, three derivatives that were twice more potent than telmisartan itself were selected for further analysis. The new derivatives induced mitochondrial fragmentation, generation of the mitochondrial reactive oxygen species, and decrease of mitochondrial membrane potential in melanoma cells, the mechanism we previously shown for induction of apoptosis by telmisartan in melanoma cells. As the new derivatives showed more potent effect on melanoma cells than telmisartan these results lay a ground for further preclinical testing in melanoma.",
publisher = "Croatian Association for Cancer Research, Zagreb, Croatia",
journal = "“HDIR-6: Targeting Cancer”, The 6th Meeting of the Croatian Association for Cancer Research with International Participation, November 10-12, 2022, Book of Abstracts",
title = "Antimelanoma Potential of New Telmisartan Analogues Without AT1 Receptor Activity",
pages = "20-20",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5450"
}

Damjanović, A., Vuković, M., Vukadinović, D., Dobričić, V.,& Grahovac, J.. (2022). Antimelanoma Potential of New Telmisartan Analogues Without AT1 Receptor Activity. in “HDIR-6: Targeting Cancer”, The 6th Meeting of the Croatian Association for Cancer Research with International Participation, November 10-12, 2022, Book of Abstracts
Croatian Association for Cancer Research, Zagreb, Croatia., 20-20.
https://hdl.handle.net/21.15107/rcub_farfar_5450

Damjanović A, Vuković M, Vukadinović D, Dobričić V, Grahovac J. Antimelanoma Potential of New Telmisartan Analogues Without AT1 Receptor Activity. in “HDIR-6: Targeting Cancer”, The 6th Meeting of the Croatian Association for Cancer Research with International Participation, November 10-12, 2022, Book of Abstracts. 2022;:20-20.
https://hdl.handle.net/21.15107/rcub_farfar_5450 .

Damjanović, Ana, Vuković, Miodrag, Vukadinović, Dragana, Dobričić, Vladimir, Grahovac, Jelena, "Antimelanoma Potential of New Telmisartan Analogues Without AT1 Receptor Activity" in “HDIR-6: Targeting Cancer”, The 6th Meeting of the Croatian Association for Cancer Research with International Participation, November 10-12, 2022, Book of Abstracts (2022):20-20,
https://hdl.handle.net/21.15107/rcub_farfar_5450 .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vukadinović, Dragana
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4110
AB  - Eight 17b-carboxamide glucocorticoids with local anti-inflammatory activity were selected and their retention behavior tested in six RP-HPLC systems (I–VI). logkw, a, and 40 parameters were calculated and correlation with previously determined logPo/w values was examined. RP-HPLC system IV, which consisted of cyano column and methanol–water mobile phases (50:50, 60:40, 70:30, and 80:20, v/v), was selected as the most reliable for lipophilicity prediction and used for the analysis of chromatographic behavior of remaining fourteen 17b-carboxamide glucocorticoids. Quantitative structure-retention re- lationships analysis was performed and PLS(logkw) model was selected as the most statistically sig- nificant. On the basis of selected model and interpretation of corresponding descriptors, new derivatives with higher logkw values and higher expected lipophilicity were designed.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis
VL  - 34
IS  - 2
SP  - 130
EP  - 137
DO  - 10.1556/1326.2021.00893
ER  - 

@article{
author = "Dobričić, Vladimir and Bošković, Jelena and Vukadinović, Dragana and Vladimirov, Sote and Čudina, Olivera",
year = "2022",
abstract = "Eight 17b-carboxamide glucocorticoids with local anti-inflammatory activity were selected and their retention behavior tested in six RP-HPLC systems (I–VI). logkw, a, and 40 parameters were calculated and correlation with previously determined logPo/w values was examined. RP-HPLC system IV, which consisted of cyano column and methanol–water mobile phases (50:50, 60:40, 70:30, and 80:20, v/v), was selected as the most reliable for lipophilicity prediction and used for the analysis of chromatographic behavior of remaining fourteen 17b-carboxamide glucocorticoids. Quantitative structure-retention re- lationships analysis was performed and PLS(logkw) model was selected as the most statistically sig- nificant. On the basis of selected model and interpretation of corresponding descriptors, new derivatives with higher logkw values and higher expected lipophilicity were designed.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis",
volume = "34",
number = "2",
pages = "130-137",
doi = "10.1556/1326.2021.00893"
}

Dobričić, V., Bošković, J., Vukadinović, D., Vladimirov, S.,& Čudina, O.. (2022). Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(2), 130-137.
https://doi.org/10.1556/1326.2021.00893

Dobričić V, Bošković J, Vukadinović D, Vladimirov S, Čudina O. Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis. in Acta Chromatographica. 2022;34(2):130-137.
doi:10.1556/1326.2021.00893 .

Dobričić, Vladimir, Bošković, Jelena, Vukadinović, Dragana, Vladimirov, Sote, Čudina, Olivera, "Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis" in Acta Chromatographica, 34, no. 2 (2022):130-137,
https://doi.org/10.1556/1326.2021.00893 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Vukadinović, Dragana
AU  - Jančić-Stojanović, Biljana
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3002
AB  - Analytical quality by design (AQbD)-oriented liquid chromatographic method development for determination of telmisartan and its impurities A, C, and 1 is determination is presented. Step-by-step process was conducted in order to define reliable design space. At the beginning, critical process parameters with the highest influence on method performance were defined: acetonitrile content in the first (ACN 1) and second (ACN 2) gradient step and time (t (2)) the second gradient step. These factors were varied according to Box-Behnken plan of experiments and their influence on retention times of impurities A and C, S value between telmisartan and impurity 1 and peak capacity were followed. In this way, the relationship between the critical process parameters and critical quality attributes was established. The obtained mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing, and the method was validated to verify the adequacy of selected optimal conditions. Finally, all validation parameters were tested, and adequacy of the method was confirmed. Applicability as a routine method was confirmed by analysis of commercially available tablets.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - AQbD-Oriented Development of a New LC Method for Simultaneous Determination of Telmisartan and Its Impurities
VL  - 80
IS  - 8
SP  - 1199
EP  - 1209
DO  - 10.1007/s10337-017-3330-2
ER  - 

@article{
author = "Dobričić, Vladimir and Vukadinović, Dragana and Jančić-Stojanović, Biljana and Vladimirov, Sote and Čudina, Olivera",
year = "2017",
abstract = "Analytical quality by design (AQbD)-oriented liquid chromatographic method development for determination of telmisartan and its impurities A, C, and 1 is determination is presented. Step-by-step process was conducted in order to define reliable design space. At the beginning, critical process parameters with the highest influence on method performance were defined: acetonitrile content in the first (ACN 1) and second (ACN 2) gradient step and time (t (2)) the second gradient step. These factors were varied according to Box-Behnken plan of experiments and their influence on retention times of impurities A and C, S value between telmisartan and impurity 1 and peak capacity were followed. In this way, the relationship between the critical process parameters and critical quality attributes was established. The obtained mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing, and the method was validated to verify the adequacy of selected optimal conditions. Finally, all validation parameters were tested, and adequacy of the method was confirmed. Applicability as a routine method was confirmed by analysis of commercially available tablets.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "AQbD-Oriented Development of a New LC Method for Simultaneous Determination of Telmisartan and Its Impurities",
volume = "80",
number = "8",
pages = "1199-1209",
doi = "10.1007/s10337-017-3330-2"
}

Dobričić, V., Vukadinović, D., Jančić-Stojanović, B., Vladimirov, S.,& Čudina, O.. (2017). AQbD-Oriented Development of a New LC Method for Simultaneous Determination of Telmisartan and Its Impurities. in Chromatographia
Springer Heidelberg, Heidelberg., 80(8), 1199-1209.
https://doi.org/10.1007/s10337-017-3330-2

Dobričić V, Vukadinović D, Jančić-Stojanović B, Vladimirov S, Čudina O. AQbD-Oriented Development of a New LC Method for Simultaneous Determination of Telmisartan and Its Impurities. in Chromatographia. 2017;80(8):1199-1209.
doi:10.1007/s10337-017-3330-2 .

Dobričić, Vladimir, Vukadinović, Dragana, Jančić-Stojanović, Biljana, Vladimirov, Sote, Čudina, Olivera, "AQbD-Oriented Development of a New LC Method for Simultaneous Determination of Telmisartan and Its Impurities" in Chromatographia, 80, no. 8 (2017):1199-1209,
https://doi.org/10.1007/s10337-017-3330-2 . .