Design, synthesis and molecular modelling studies of new triazol derivatives as aromatase inhibitors

In this study, 4-(2-((1H-1,2,4-triazol-3-yl)thio)acetyl)benzonitrile compound was obtained by adding 2'-bromo-4-cyano-acetophenone compound to 1H-1,2,4 triazole-3-thiol compound. In the second step, by reducing this compound with NaBH4, 4-(2-((1H-1,2,4-triazol-3-yl)thio)-1-hydroxyethyl)benzonitrile compound was obtained. In the last step, by substituting 2-bromoacetophenone derivatives, new triazole structure compounds (3a-3n) were obtained. Toxicity effects of 3a-3n compounds on MCF-7, which is positive for estrogen receptor, and inhibitory activities on aromatase enzyme were investigated. As a result of cytotoxicity studies, compounds 3i, 3g, 3m and 3n were found to effectively inhibit the aromatase enzyme and were found to be 8.59 µM, 11.98 µM, 11.41 µM and 7.69 µM, respectively. In addition, molecular docking studies were performed for these compounds and their possible bonds with the aromatase enzyme were determined. The studies were also supported by ADME studies performed on the compounds.