New imidazole derivatives as aromatase inhibitor: Design, synthesis, biological activity, molecular docking, and computational ADME-Tox studies

Abstract

In this study, a series of imidazole derivatives was designed, synthesized, and evaluated for in vitro bi- ological activity on the human breast cancer cell line MCF7 by MTT assay. To determine the selectivity of the compounds, their cytotoxic effects on the L929 (healthy mouse fibroblast) cell line were also in- vestigated. Compounds 1a, 1b , and 1d were found to be more effective than the reference drug cisplatin against the MCF7 cell line. It is seen that the cytotoxic effects of the compounds on the L929 cell line are quite low, and the compounds are found to be highly selective. The inhibition potentials of the com- pounds 1a, 1b, 1d , and 1k which were effective on the MCF7 cell line, and on the aromatase enzyme were evaluated and it was found that the compounds had similar effects to the reference drug letro- zole. Further, the interactions between the best active compounds and the human aromatase cytochrome P450 (CYP) enzyme were analyzed through a molecular docking study. The findings suggest that these compounds could be a promising candidate for the creation of a new family of non-steroidal aromatase inhibitors. Finally, computational ADME-Tox studies of compounds 1a, 1b, 1d , and 1k were performed and found to have the appropriate profile.