‘4-Aminoquinazoline-6, 7-diol’ derivatives for enhanced EGFR binding (as inhibitor) against Lung cancer

Abstract

ABSTRACTThe Epidermal growth factor receptor (EGFR) have been considered as potential targets for cancer therapy due to their role in regulating proliferation and survival of cancer cells. In the present study, the four ‘4-aminoquinazoline-6, 7-diol’ derivative molecules were selected to the theoretically investigate their inhibitory activity against EGFR protein. Molecules were evaluated on the basis of: (i) in-silico cytotoxic assay on human cancer cell lines expressing EGFR (A549 and A431), (ii) in-silico kinase assay, (iii) impact of molecular interaction on EGFR, (iv) molecular interaction stability, (v) inhibitory impact of molecules on combined expression of EGF-EGFR and (v) ADME observations. Studies were observed on the scale of two known EGFR inhibitors. In-silico cytotoxicity screening results demonstrated that the A431 lung cancer cell line was vulnerable to compound abc1-4. However, A549 cells were less sensitive to our designed molecules. From kinase inhibition assay results, compound abc1&2 were found to be an inhibitor against EGFR. According to the molecular interaction analysis, compounds abc1-4 performed in similar fashion of positive controls, acting at the catalytic site of EGFR. Altogether, these potent compounds, with compromised bioavailability, could likely be developed as a promising EGFR targeted drug(s) for cancer therapy.