Synthesis and Antiproliferative Activity Evaluation of Novel 2,4,6-Trisubstituted Pyrimidine Derivatives

In order to find new and efficient anti-tumor drugs, a series of 2,4,6-trisubstituted pyrimidine derivatives were designed and synthesized, and the antiproliferative activities were evaluated against four cancer cell lines of PC-3 (human prostate cancer cells), MGC-803 (human gastric cancer cells), MCF-7 (human breast cancer cells) and HGC-27 (human gastric carcinoma cell line) using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most of the compounds exhibited moderate to potent antiproliferative activities against the four human tumor cell lines, among which N-(3-(2-((4-((1,3,4-thiadiazol-2-yl)thio)-6-(trifluoromethyl)pyrimidin 2yl)thio)acetamido)phenyl)acrylamide (19q) had the best inhibitory activity against PC-3 cells with IC50 value of (0.87 +/- 0.15) mu mol center dot L-1, the antitumor activity was significantly better than the positive control 5-fluorouracil. Further anti-tumor mechanism studies showed that compound 19q could induce apoptosis in PC-3 cells. In addition, compound 19q might play an anti-tumor effect by down-regulating the expression of anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic proteins Bax and p53.