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 (EGFR-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 3-fluoro--(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound could closely form many hydrogen bonds with EGFR-TK. Therefore, compound is potential to develop as novel anti-cancer drug.