Designing and In silico Studies of Novel Hybrid of 1,3,4-oxadiazole-chalcone Derivatives as EGFR Inhibitors.

Abstract

The tyrosine kinase epidermal growth factor receptor (TK-EGFR) has recently been identified as a useful target for anticancer treatments. The major concern for current EGFR inhibitors is resistance due to mutation, which can be overcome by combining more than one pharmacophore into a single molecule. In the present study, various hybrids of 1,3,4-oxadiazole-chalcone derivatives were gauged for their EGFR inhibitory potential. The design of 1,3,4-oxadiazole-chalcone hybrid derivatives was carried out and in-silico studies, viz., molecular docking, ADME, toxicity, and molecular simulation, were performed as EGFR inhibitors. Twenty-six 1,3,4-oxadiazole-chalcone hybrid derivatives were designed using the combi-lib tool of the V life software. AutoDock Vina software was used to perform in silico docking studies, while SwissADME and pkCSM tools were used to analyse molecules for ADME and toxicity. Desmond software was used to run the molecular simulation. Around 50% of molecules have shown better binding affinity as compared to standard and co-crystallized ligands. Molecule 11 was found to be a lead molecule that has the highest binding affinity, good pharmacokinetics, good toxicity estimates and better protein-ligand stability.