MOLECULAR MODELING STUDIES OF NOVEL N-(3-(BENZO[D]THIAZOL-2-YL)-4-((SUBSTITUTED BENZYL) OXY)PHENYL) ACETAMIDE AS EGFR INHIBITORS

Background: Cancer is continuing to be a major health problem in developing as well as undeveloped countries. It is a leading cause of mortality worldwide, accounting for most of the deaths. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, and mutations that lead to EGFR overexpression or overactivity have been associated with a variety of human cancers. Purpose: In-silico design of EGFR inhibitors by inhibiting EGFR kinase activity which competes with its cognate ligands, and it may potentially constitute a new class of effective drugs in cancer therapy. Experimental work: In the present investigation, we have performed a similarity/sub-structure-based search of eMolecule database and find out promising benzothiazole derivatives as EGFR inhibitors by several screening criteria, including molecular docking and pharmacokinetics features. Result and Discussion: Molecular docking clearly showed that the final proposed derivatives potential to form a number of binding interactions. Molecular dynamics simulation studies showed that the EGFR protein becomes stable when proposed derivatives bind to the receptor cavity. Strong binding affinity was found for all molecules towards the EGFR, which was substantiated by the binding energy calculation using the MM-PBSA approach. Conclusion: The compounds with higher selectivity and great potential H6 and H7 have been reported, and it can be concluded that proposed molecules may be potential and safer chemical agents for therapeutic application in cancer therapy.