Design, synthesis and antitumor activity evaluation in vitro of 4,6,7-trisubstituted quinazoline derivatives containing acrylamide moiety

Abstract In order to search for new antitumor drugs with high efficiency, a series of novel quinazoline derivatives containing acrylamide group were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines (PC-3, H1975, A549 and Eca-109) using MTT assay in vitro. Among them, compound N-(3-((6-((4-cyanobenzyl)oxy)-7-methoxyquinazolin-4-yl)amino)phenyl)acrylamide ( 14m ) showed good anti-tumor proliferation activity against four tested cancer cell lines, with IC 50 values of 1.09 ± 0.04µM to H1975 cell. The antitumor activity was significantly better than that of 5-FU . Further mechanism studies showed that compound 14m inhibit the proliferation and migration of H1975 cells, block its cell cycle at G2/M phase and induce its apoptosis in a concentration dependent and time-dependent manner.