Citation: Li Erdong, Meng Yaqi, Zhang Luye, Zhang Yang, Zhou Rui, Liu Limin, Li Nab, Xin Jingchao, Zheng Jiaxin, Shan Lihong, Liu Hongmin, Zhang Qiurong. Synthesis and Antitumor Evaluation of 2, 4, 6-Trisubstituted Pyrimidine Derivatives Containing Benzothiazole Moiety[J]. Chinese Journal of Organic Chemistry, ;2020, 40(2): 417-422. doi: 10.6023/cjoc201907016 shu

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

Li Erdong ^a,d ,
Meng Yaqi ^a,d ,
Zhang Luye ^a,b ,
Zhang Yang ^a,b ,
Zhou Rui ^a ,
Liu Limin ^a ,
Li Nab ^b,c ,
Xin Jingchao ^b,c ,
Zheng Jiaxin ^a,d ,
Shan Lihong ^a,b,c,d,, ,
Liu Hongmin ^a,b,c,d,, ,
Zhang Qiurong ^a,b,c,d,,

a.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
c.
Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001
d.
Key Laboratory of Technology of Drug Preparation, Ministry of Education, Zhengzhou 450001

Corresponding author: Shan Lihong, 343785851@qq.com Liu Hongmin, liuhm@zzu.edu.cn Zhang Qiurong, zqr409@yeah.net
Received Date: 8 July 2019
Revised Date: 14 October 2019
Available Online: 25 February 2019
Fund Project: Project supported by the National Natural Science Foundation of China (No. U1904163) and the National Key Research Program of Proteins (No. 2018YFE0195100)the National Key Research Program of Proteins 2018YFE0195100the National Natural Science Foundation of China U1904163

Figures(2)

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.
- pyrimidine,
- benzothiazole,
- synthesis,
- antitumor activity
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