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 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 IC50 = 0.032 ± 0.042 µM, compared to IC50 = 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.
['Acar Çevik|Ulviye|U|', 'Kaya Çavuşoğlu|Betül|B|', 'Sağlık|Begüm Nurpelin|BN|', 'Osmaniye|Derya|D|', 'Levent|Serkan|S|0000-0003-3692-163X', 'Ilgın|Sinem|S|', 'Özkay|Yusuf|Y|0000-0001-8815-153X', 'Kaplancıklı|Zafer Asım|ZA|0000-0003-2252-0923']
D000970:Antineoplastic Agents D047072:Aromatase Inhibitors D001562:Benzimidazoles D001932:Brain Neoplasms D049109:Cell Proliferation D002470:Cell Survival D006801:Humans D000077289:Letrozole D061986:MCF-7 Cells D062105:Molecular Docking Simulation
docking triazolothiadiazine aromatase MCF-7 ADME NIH3T3 benzimidazole