摘要/Abstract
为了寻找高效的抗肿瘤药物，设计并合成了一系列含苯并噻唑砌块的2，4，6-三取代嘧啶衍生物.采用噻唑蓝（MTT）法对目标化合物在人类四种癌细胞[EC-109（人食管癌细胞）、MGC-803（人胃癌细胞）、PC-3（人前列腺癌细胞）、HepG-2（人肝癌细胞）]、GES-1（人正常胃黏膜上皮细胞）和HEEC（人正常食管细胞）中进行抗肿瘤活性评价，结果显示部分化合物对MGC-803和PC-3细胞表现出中度至强效的抗肿瘤活性.其中2-（（（4-（4-（吡啶-2-基）哌嗪-1-基）-6-（三氟甲基）嘧啶-2-基）硫基）甲基）苯并[d]噻唑（13h）和2-（（（4-（4-（嘧啶-2-基）哌嗪-1-基）-6-（三-氟甲基）嘧啶-2-基）硫代）甲基）苯并[d]噻唑（13i）对PC-3表现出比较好的抗肿瘤活性，IC50值分别3.82和2.29μmol/L，且化合物13h和13i对GES-1的细胞增值毒性明显小于阳性对照5-氟尿嘧啶.
关键词: 嘧啶, 苯并噻唑, 合成, 抗肿瘤活性
In order to find high-efficiency antitumor drugs, a series of 2,4,6-trisubstituted pyrimidine derivatives containing benzothiazole moiety were designed, synthesized and evaluated for antitumor activities against four cancer cells (EC-109, human esophageal cancer cells; MGC-803, human gastric cancer cells; PC-3, human prostate cancer cells; HepG-2, human liver cancer cells), GES-1 (human normal gastric mucosal epithelial cells), and HEEC (human normal esophagus) using thiazolyl blue (MTT) method. The results showed that some compounds exhibited moderate to strong antitumor activities against MGC-803 and PC-3 cells. Among them, 2-(((4-(4-(pyridin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)-thio)methyl)benzo[d]thiazole (13h) and 2-(((4-(4-(pyrimidin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-methyl)benzo[d]thiazole (13i) showed the most potent antitumor activities against PC-3 cells with IC50 values of 3.82 and 2.29 μmol/L, respectively. The toxicities of compounds 13h and 13i to GES-1 cells were significantly lower than the positive control 5-fluorouracil.
Key words: pyrimidine, benzothiazole, synthesis, antitumor activity
PDF全文下载地址:
点我下载PDF
