Aromatase (CYP19), a member of cytochrome P450 enzymes, is a monooxygenase responsible for the conversion of androgens (androstenedione and testosterone) to estrogens (estradiol and estrone). Estrogens play a central role in the development and progression of breast cancer: aromatase inhibitors and antiestrogens represent first line treatments in post-menopausal estrogen-dependent breast cancer. Extensive research over the last decades led to the identification of several aromatase inhibitors, classified as steroidal and non-steroidal, acting by a competitive or not competitive mechanism of action.

Our research group is involved in the discovery of novel non-steroidal aromatase inhibitors, based on azole scaffold. In the present study, novel compounds were designed by modification of BAS02077837, an imidazole-based aromatase inhibitor. Synthesized molecules were evaluated against aromatase, in a fluorimetric in vitro assay, and compared to letrozole. The most active derivatives were then submitted to cell viability and cytotoxicity evaluation on MCF7 breast cancer cells. Docking studies were also performed on most promising compounds to shed light on their binding mode in human aromatase binding pocket.