Design, synthesis and biological evaluation of imidazole and triazole-based carbamates as novel aromatase inhibitors

In the search for novel aromatase inhibitors, a series of triazole and imidazole-based carbamate derivatives were designed and synthesized. Final compounds were thus evaluated against human aromatase by in vitro kinetic experiments in a fluorimetric assay in comparison with letrozole. The effect of most active derivatives 13a and 15c was then evaluated in vitro on the human breast cancer cell line MCF7 by MTT assay, cytotoxicity assay (LDH release) and cell cycle analysis, revealing a dose-dependent inhibition profile of cell viability and low micromolar IC50 values. In addition, docking simulations were also carried out to elucidate at a molecular level of detail the binding modes adopted to target human aromatase. (C) 2020 Elsevier Masson SAS. All rights reserved.

Automated summary

Novel aromatase inhibitors based on triazole and imidazole-based carbamate derivatives were designed and synthesized, with compounds 13a and 15c showing dose-dependent inhibition of cell viability on the human breast cancer cell line MCF7. Docking simulations were also carried out to elucidate the binding modes of these active compounds to target human aromatase at a molecular level.