Affiliation:
1. AISSMS College of Pharmacy, Kennedy Road, Pune 01, Maharashtra, India
Abstract
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.
Publisher
Bentham Science Publishers Ltd.