Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

Abstract

In pursuit of an anticancer lead, a library of 1,2,3-triazole derivatives (7a-x) was prepared, characterized and screened for in vitro cytotoxicity in different cell lines. Most of the compounds proved to be cytotoxic with IC50 values in the low micromolar range. Further studies showed that the most active compound 7c induces caspase-dependent apoptosis in Jurkat cells by activating both the intrinsic and the extrinsic apoptotic pathways and perturbs cell-cycle progression. Moreover, 7c did not show any genotoxic activity. Molecular docking simulations were performed against epidermal growth factor receptor (EGFR). Docking experiments showed that, compounds 7c, 7o and 7 v bind within active sites of epidermal growth factor receptor EGFR (Pdb ID: 6P8Q) by strong hydrogen bonds with residue MET793, Pi-Sulfur with residue MET790 and Pi-Alkyl type interactions with residues LEU788, ALA743. The SwissADME webserver investigation suggested that most of the synthesized compounds follow the rules of drug-likeness.