Abstract
Background: Cancer is a leading cause of death worldwide. EGFR is one of the important targets considered for current chemotherapeutic agents. The problem of drug resistance can be overcome by the use of hybrid molecules. A hybrid of 1,3,4-oxadiazole and chalcone has been proved to be an anti- EGFR inhibitor.
Objective: The aim of the study was to carry out pharmacophore optimization of the hybrid nucleus of 1,3,4- oxadiazole and chalcone by using literature findings and in-silico approach. A series of 24 substituted hybrid molecules of 2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)-N-(4-((Z)-3-phenylacryloyl)phenyl)acetamide derivatives were subjected to 2D and 3D QSAR studies.
Methods: The survey of literature was carried out for selected hybrid nucleus using different available databases. The 2D QSAR was performed by using the MLR, PLS, and PCR methods, while 3D QSAR was performed using the KNN-MFA method.
Results: A summary of literature findings was prepared. For 2D QSAR, statistically significant model was obtained for the MLR method with r2=0.9128, q2=0.8065. For the 3D QSAR model, I was found to be significant with q2=0.834. The pharmacophoric requirements for inhibition of EGFR were optimized by use of the evidence attained after the generation of descriptors from QSAR studies and literature findings.
Conclusion: This optimized pharmacophore will be useful in further drug design process.
Keywords: EGFR inhibitors, quantitative structure activity relationship, 1, 3, 4-oxadiazole-chalcone hybrid, pharmacophore optimization, in silico studies, chemotherapeutic agents.
Graphical Abstract
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