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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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/7/1642 |
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| author | Ulviye Acar Çevik Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Serkan Levent Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı |
| author_facet | Ulviye Acar Çevik Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Serkan Levent Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı |
| author_sort | Ulviye Acar Çevik |
| collection | DOAJ |
| 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 <b>5c</b>, <b>5e</b>, <b>5k</b>, and <b>5m</b> 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 <b>5e</b> showed slight less potent aromatase inhibitory activity than that of letrozole with IC<sub>50</sub> = 0.032 ± 0.042 µM, compared to IC<sub>50</sub> = 0.024 ± 0.001 µM for letrozole. Furthermore, compound <b>5e</b> 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 (<b>5a</b>–<b>5p</b>) were calculated by QikProp 4.8 software. |
| first_indexed | 2024-03-10T20:43:22Z |
| format | Article |
| id | doaj.art-db1d871726b443aaade27af80f3b145b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:43:22Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-db1d871726b443aaade27af80f3b145b2023-11-19T20:32:51ZengMDPI AGMolecules1420-30492020-04-01257164210.3390/molecules25071642Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase InhibitorUlviye Acar Çevik0Betül Kaya Çavuşoğlu1Begüm Nurpelin Sağlık2Derya Osmaniye3Serkan Levent4Sinem Ilgın5Yusuf Özkay6Zafer Asım Kaplancıklı7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Bülent Ecevit University, Zonguldak 67100, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyIn 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 <b>5c</b>, <b>5e</b>, <b>5k</b>, and <b>5m</b> 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 <b>5e</b> showed slight less potent aromatase inhibitory activity than that of letrozole with IC<sub>50</sub> = 0.032 ± 0.042 µM, compared to IC<sub>50</sub> = 0.024 ± 0.001 µM for letrozole. Furthermore, compound <b>5e</b> 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 (<b>5a</b>–<b>5p</b>) were calculated by QikProp 4.8 software.https://www.mdpi.com/1420-3049/25/7/1642aromataseMCF-7NIH3T3benzimidazoletriazolothiadiazinedocking |
| spellingShingle | Ulviye Acar Çevik Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Serkan Levent Sinem Ilgın Yusuf Özkay Zafer Asım Kaplancıklı Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor Molecules aromatase MCF-7 NIH3T3 benzimidazole triazolothiadiazine docking |
| 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 | aromatase MCF-7 NIH3T3 benzimidazole triazolothiadiazine docking |
| url | https://www.mdpi.com/1420-3049/25/7/1642 |
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