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

• DOI: 10.1016/j.ejmech.2020.113115
• Publication Date: 2020-12-25T07:38:03Z
• Authors: Alessandra Ammazz...; Marialucia Gallorini; Marialuigia Fanta...; Nicola Gambacorta; Barbara De Filippis; Letizia Giampietro; Cristina Maccallini; Orazio Nicolotti; Amelia Cataldi; Rosa Amoroso
• Keywords: 0301 basic medicine; Molecular Structure; Aromatase Inhibitors; Imidazoles; 610; Cytochrome P450; Aromatase inhibitor; Aromatase inhibitors; Breast cancer; Carbamates; Cytochrome P450; Imidazole; Triazole; Triazoles; 620; 3. Good health; 03 medical and health sciences; Breast cancer; Drug Design; Carbamate; Humans; Triazole; Carbamates; Imidazole

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.