Exploring Anticancer Potential of Virtually Designed Novel Quinazoline Derivatives as EGFR Inhibitors: An In-silico Approach

Introduction: Cancer is a dreadful illness caused by uncontrolled cell growth. Several studies have demonstrated that the overexpression of growth factors and receptors, the triggering of oncogenes, and the deactivation of tumor suppressor genes are the primary reasons for aggressive and resistant forms of cancer. The epidermal growth factor receptor (EGFR) is one such receptor that is targeted by medications to treat cancer. In this work, we attempted to create novel compounds that will function as EGFR inhibitors by using the molecular structure of 4-amino-7-methoxy quinazoline as a template. Methodology: A covalent molecular docking investigation was carried out by introducing several functional groups to the template of 4-amino-7-methoxy quinazoline, and evaluating the binding capacity of all ligands to the target domains. Using ADME analysis and DFT study, the potential of proposed compounds for additional in vitro and in vivo experiments was assessed. Results: Based on the generated results, the addition of N- (pyrimidin-4-yl) acrylamide at C-4 and the addition of (E)-N-methyl-4-(piperidin-1-yl) but-2-enamide at C-6 of 4- amino-7-methoxy quinazoline enhanced the binding affinity of the designed compound to the targeted protein efficiently. Discussion: The findings we reported demonstrated that the virtually designed S10 could block EGFR; hence, this S10 molecule is a noteworthy inhibitor of EGFR TK. Conclusion: Thus, the proposed compound S10 quinazoline derivative has the potential to be a lead compound for future preclinical development, providing a viable therapeutic approach for targeting EGFR-driven cancer with overcoming resistance mechanisms.