含苯并噻唑砌块的2,4,6-三取代嘧啶衍生物的合成及抗肿瘤活性评价(英文)  

Synthesis and Antitumor Evaluation of 2,4,6-Trisubstituted Pyrimidine Derivatives Containing Benzothiazole Moiety

作　　者：李二冬 孟娅琪 张路野 张洋 周蕊 刘丽敏 栗娜 辛景超 郑甲信[1,4] 单丽红 刘宏民[1,2,3,4] 张秋荣 Li Erdong;Meng Yaqi;Zhang Luye;Zhang Yang;Zhou Rui;Liu Limin;Li Na;Xin Jingchao;Zheng Jiaxin;Shan Lihong;Liu Hongmin;Zhang Qiurong(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou 450001;Key Laboratory of Henan Province for Drug Quality and Evaluation,Zhengzhou 450001;Key Laboratory of Technology of Drug Preparation,Ministry of Education,Zhengzhou 450001)

机构地区：[1]郑州大学药学院,郑州450001 [2]新药创制与药物安全性评价河南省协同创新中心,郑州450001 [3]河南省药物质量评价重点实验室,郑州450001 [4]教育部药物制备关键技术重点实验室,郑州450001

出　　处：《有机化学》2020年第2期417-422,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.U1904163);蛋白关键研究(No.2018YFE0195100)资助项目.

摘　　要：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)、Hep G-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.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(13 h) and 2-(((4-(4-(pyrimidin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-methyl)benzo[d]thiazole(13 i) showed the most potent antitumor activities against PC-3 cells with IC50 values of 3.82 and 2.29μmol/L, respectively. The toxicities of compounds 13 h and 13 i to GES-1 cells were significantly lower than the positive control 5-fluorouracil.

关 键 词：嘧啶 苯并噻唑 合成 抗肿瘤活性 

分 类 号：O626[理学—有机化学] TQ463.5[理学—化学]