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

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 caspasedependent 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.

Automated summary

This study focused on the synthesis of a library of 1,2,3-triazole derivatives and their screening for cytotoxicity against various cell lines. Compound 7c was identified as the most active one, inducing apoptosis in Jurkat cells through both intrinsic and extrinsic pathways and disrupting cell cycle progression. Molecular docking simulations revealed its binding to the active sites of EGFR, indicating potential for further development as a lead compound for anticancer drugs.