Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells. (1st January 2021)

• Record Type: Journal Article
• Authors: Zhang, Yan; Wang, Qin; Li, Luolan; Le, Yi; Liu, Li; Yang, Jing; Li, Yongliang; Bao, Guochen; Yan, Longjia
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 1205
• Page End: 1216
• Publication Date: 2021-01-01
• Subjects: Quinazolinone -- EGFR -- kinase inhibitor -- structure-activity relationship -- antiproliferative; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.1933466
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: 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 wt -TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro- N -(4-((3-methyl-4-oxo-3, 4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d 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 4d could closely form many hydrogen bonds with EGFR wt -TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug.