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

Background: 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.

Aim and objective: In the present study, various hybrids of 1,3,4-oxadiazole-chalcone derivatives were gauged for their EGFR inhibitory potential.

Method: 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 combilib 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.

Result: Around 50% of molecules have shown better binding affinity as compared to standard and cocrystallized ligands.

Conclusion: 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.