Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Thiazole Structure

A series of 2,4,6-trisubstituted quinazoline derivatives containing thiazole group were designed and synthesized, and their antiproliferative activities against human tumor cell lines (PC-3, H1975, MGC-803 and A549) were determined. 3-((2-(((2-chlorothiazol-5-yl)methyl)thio)-6-methoxyquinazolin-4-yl)amino)benzonitrile (14i) was identified as the most potent compound in antiproliferation against MGC-803 cells, with the value was (4.54 +/- 0.32) mu mol/L, which was better than the positive control 5-fluorouracil (5-FU) [(8.14 +/- 0.68) mu mol/L]. Further mechanistic studies showed that compound 14i could inhibit the clonal proliferation and migration of MGC-803 cells. In addition, compound 14i could induce apoptosis of MGC-803 cells and arrest the cell cycle at late period of DNA synthesis/mitotic phase (G2/M) phase. These results indicated that compound 14i could as a potential antitumor drug.