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 .