Facile synthesis of two azete-steroid derivatives and theoretical evaluation of its interaction with the aromatase enzyme

Abstract

Several aromatase inhibitors have used for the treatment of breast cancer; however, some of these drugs may produce some side effects such as endometrial cancer and bone loss. The aim of this study was to synthesize two new azete-steroid derivatives (compounds 9 or 10) to evaluate its theoretical interaction with an aromatase enzyme (2wd3) using anastrozole and exemestane as controls in a docking model. The preparation of 9 and 10 was carried out using a series of reactions which involves amination, etherification, nitration, and addition. Chemical structure of the compounds was confirmed using elemental analysis and NMR spectrum. The results showed that compounds 9 or 10 could bind to a different type of aminoacid residues involved in of 2wd3 protein surface compared anastrozole and exemestane; this phenomenon may exert changes in the biological activity of aromatase enzyme. All data suggest that compounds 9 or 10 could be an alternative for the treatment of breast cancer.