In silico ADMET screening & molecular docking of some 1-(5-(4-chlorophenyl)-1,3,4-oxadiazol-3(2H)-yl) ethanone derivatives to be developed as triple mutant T790M/C797S EGFR inhibitors
Keywords:
EGFR, angiogenesis, cancer, ADMET, molecular dockingAbstract
EGFRs' high expression and/or adaptive activation coincides with the pathogenesis and development of many tumors, making them appealing candidates for both diagnosis and therapy. Several strategies for targeting these receptors and/or the EGFR-mediated effects in cancer cells have been established. A lot of in silico models are developed for prediction of chemical ADMET properties. However, it is still not easy to evaluate the drug-likeness of compounds in terms of so many ADMET properties. In present study, we have designed some 1-(5-(4-chlorophenyl)-1, 3, 4-oxadiazol-3(2H)-yl) ethanone derivatives to be developed as potential EGFR inhibitors for the treatment of cancer. The designed derivatives were screened through Lipinski rule, Veber’s rule, ADMET analysis, drug-likeness properties and molecular docking. We concluded that all the compounds sm1, sm2, sm3, sm8, sm9, sm10, sm11, sm12, sm13, sm14, sm15, sm18, and sm19 were found to possess drug-likeness properties and therefore were subjected for molecular docking studies. From molecular docking studies it was observed that Molecules Sm3, Sm8, Sm9, Sm10, Sm12, and Sm2 had formed either three or two conventional hydrogen bonds with EGFR enzyme and hence selected for synthesis which can be developed further to get more promising molecules for the treatment of cancer.
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