4-Aminoquinazoline-6, 7-diol Derivatives for Enhanced EGFR Binding (as Inhibitor) Against Lung Cancer

Epidermal growth factor receptor (EGFR) is one of the potential targets for cancer therapy because it regulates the proliferation and survival of cells. In the present study, four ‘4-aminoquinazoline-6, 7-diol’ derivative molecules were computationally investigated for their inhibitory activity against EGFR protein. Methods: Molecules were evaluated based on (i) in-silico cytotoxic assay defined for 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 the 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 affected by compound Cmp1-4. However, A549 cells were less sensitive to Cmp1-4. Kinase inhibition assay resulted in compounds Cmp1 and 2 inhibiting EGFR. According to the molecular interaction analysis, compound Cmp1-4 was performed similarly to positive control, acting at the catalytic site of EGFR. Altogether, with compromised bioavailability, these potent compounds could likely be developed as promising EGFR-targeted drug(s) for cancer therapy.