Design, synthesis, in vitro and in silico studies of some novel triazoles as anticancer agents for breast cancer

Abstract Against the increasing incidence of breast cancer in postmenopausal women in recent years, a few clinically approved inhibitors and their side-effect profiles indicate the need for the development of new aromatase inhibitors. In this study, carried out to develop a new aromatase inhibitor, the triazole ring system was preferred because of its known activity in the field. The triazole ring, which is in the structure of the most commonly used aromatase inhibitors such as anastrazole and letrazole, was synthesized from the thiourea residue. Inhibitor structures were elucidated using the 1H-NMR, 13C-NMR, 2D-NMR, and HRMS spectroscopic methods. A cytotoxicity (MTT) test was performed to determine the anticancer activity of the compounds on breast (MCF7) carcinoma cell type. In addition, to determine selectivity of their action, the final compounds were screened against a healthy NIH3T3 cell line (mouse embryonic fibroblast cells). In terms of the MTT assay, it was observed that the calculated IC50 values of compound 5e for the NIH3T3 cell line were found to be higher than for the MCF7 cell lines. Considering the viability results, it was found that the selected compound 5e showed a favorable safety profile and that it has anticancer activities. It was determined by in vitro studies that compound 5e showed inhibition potential on the aromatase enzyme with an IC50 = 0.028 μM value. The docking study of compound 5e revealed that there is a strong interaction between the active sites of the human aromatase enzyme and the analyzed compound.