Design, Synthesis, and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Acrylamide

In order to discover novel and effective anti-tumor drugs, a series of new 2,4,6-trisubstituted quinazoline derivatives containing acrylamide structure have been designed, synthesized and evaluated for their antitumor activity against six human tumor cell lines (PC-3, Eca-109, MGC-803, HGC-27, A549 and H1975) by MTT assay, and compound N -(3-((6-methoxy-2-((3-methylbenzyl)thio)quinazolin-4-yl)amino)phenyl)acrylamide displayed the best antiproliferative activity against PC-3 cells (IC 50 = 1.28 ± 0.63 μM), which was better than the positive control Gefitinib. Further mechanism research showed that this compound could significantly inhibited the migration and colony formation of PC-3 cells. At the same time, this compound induced PC-3 cells apoptosis through increasing the expression of pro-apoptotic proteins Bax and p53 and down-regulating the anti-apoptotic protein Bcl-2. This compound could also bound tightly to the active pocket of EGFR. Collectively, our findings suggested that this compound deserves further reseach as a potent antitumor agent for cancer therapy.