Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells

In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) tumour cells (A431, A549, MCF-7, NCI-H1975). particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher activities all than Gefitinib (IC50 3.48, 2.55, 0.87 6.42 μM, respectively). Furthermore, could induce apoptosis MCF-7 arrest in G2/M phase at tested concentration. Molecular docking ADMET studies that closely form many hydrogen bonds with EGFRwt-TK. Therefore, is potential to develop as novel anti-cancer drug.