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Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor

In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthes...

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Autores principales: Acar Çevik, Ulviye, Kaya Çavuşoğlu, Betül, Sağlık, Begüm Nurpelin, Osmaniye, Derya, Levent, Serkan, Ilgın, Sinem, Özkay, Yusuf, Kaplancıklı, Zafer Asım
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180718/
https://www.ncbi.nlm.nih.gov/pubmed/32252458
http://dx.doi.org/10.3390/molecules25071642
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author Acar Çevik, Ulviye
Kaya Çavuşoğlu, Betül
Sağlık, Begüm Nurpelin
Osmaniye, Derya
Levent, Serkan
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
author_facet Acar Çevik, Ulviye
Kaya Çavuşoğlu, Betül
Sağlık, Begüm Nurpelin
Osmaniye, Derya
Levent, Serkan
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
author_sort Acar Çevik, Ulviye
collection PubMed
description In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthesized and studied as potent aromatase inhibitors. First, these compounds were tested for their anti-cancer properties against human breast cancer cell line (MCF-7). The most active compounds 5c, 5e, 5k, and 5m on MCF-7 cell line were subject to further in vitro aromatase enzyme inhibition assays to determine the possible mechanisms of action underlying their activity. Compound 5e showed slight less potent aromatase inhibitory activity than that of letrozole with IC(50) = 0.032 ± 0.042 µM, compared to IC(50) = 0.024 ± 0.001 µM for letrozole. Furthermore, compound 5e and reference drug letrozole were docked into human placental aromatase enzyme to predict their possible binding modes with the enzyme. Finally, ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds (5a–5p) were calculated by QikProp 4.8 software.
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spelling pubmed-71807182020-05-01 Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor Acar Çevik, Ulviye Kaya Çavuşoğlu, Betül Sağlık, Begüm Nurpelin Osmaniye, Derya Levent, Serkan Ilgın, Sinem Özkay, Yusuf Kaplancıklı, Zafer Asım Molecules Article In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthesized and studied as potent aromatase inhibitors. First, these compounds were tested for their anti-cancer properties against human breast cancer cell line (MCF-7). The most active compounds 5c, 5e, 5k, and 5m on MCF-7 cell line were subject to further in vitro aromatase enzyme inhibition assays to determine the possible mechanisms of action underlying their activity. Compound 5e showed slight less potent aromatase inhibitory activity than that of letrozole with IC(50) = 0.032 ± 0.042 µM, compared to IC(50) = 0.024 ± 0.001 µM for letrozole. Furthermore, compound 5e and reference drug letrozole were docked into human placental aromatase enzyme to predict their possible binding modes with the enzyme. Finally, ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds (5a–5p) were calculated by QikProp 4.8 software. MDPI 2020-04-02 /pmc/articles/PMC7180718/ /pubmed/32252458 http://dx.doi.org/10.3390/molecules25071642 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Acar Çevik, Ulviye
Kaya Çavuşoğlu, Betül
Sağlık, Begüm Nurpelin
Osmaniye, Derya
Levent, Serkan
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title_full Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title_fullStr Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title_full_unstemmed Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title_short Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor
title_sort synthesis, docking studies and biological activity of new benzimidazole- triazolothiadiazine derivatives as aromatase inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180718/
https://www.ncbi.nlm.nih.gov/pubmed/32252458
http://dx.doi.org/10.3390/molecules25071642
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