Synthesis, molecular modeling, and biological evaluation of 1,2,4-triazole derivatives containing pyridine as potential anti-tumor agents

Abstract

There is an accumulating body of experimental evidences validating focal adhesion kinase (FAK) as a therapeutic target and offering opportunities for anti-tumor drug development. In present study, we sought to synthesize twenty-eight potential FAK inhibitors as anti-tumor agents based on 1,2,4-triazole skeleton. The bioassay assays demonstrated that compounds 3e and 6j showed the most potent activity, 3e inhibited the growth of HCT116 and HepG2 cell lines with IC50 values of 8.17 and 7.04 μM, while compound 6j showed the most potent biological activity against HCT116 cell line (IC50 = 1.99 μM). Besides, compound 6j also exhibited significant FAK inhibitory activity (IC50 = 2.41 μM). The results of flow cytometry and western-blot assay demonstrated that compounds 3e and 6j possessed good anti-proliferative activity. Docking simulations were performed to position compounds 3e and 6j into the active site of FAK to determine the probable binding model.