含吲哚环2,4-二氨基嘧啶类化合物的合成及抗肿瘤活性
收稿日期: 2016-11-03
修回日期: 2016-12-19
网络出版日期: 2016-12-29
基金资助
国家自然科学基金（Nos.21102069、21372113）、广州市珠江科技新星专项（No.2012J2200051）资助项目.
Synthesis and Biological Activities of Novel 2,4-Diaminopyrimidine Derivatives Bearing Indole Moiety
Received date: 2016-11-03
Revised date: 2016-12-19
Online published: 2016-12-29
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21102069, 21372113), and the Project of Science and Technology New Star in Zhujiang Guangzhou City (No. 2012J2200051).
在课题组前期研究的基础上，设计、合成了23个未见文献报道的含吲哚结构单元的2，4-二氨基嘧啶类化合物，其结构经1H NMR，13C NMR及HRMS确认. 并采用噻唑蓝（MTT）法测试了目标化合物对人子宫颈癌细胞（HeLa）、乳腺癌细胞（MD-MBA-231）、前列腺癌细胞（PC-3）、人结肠癌细胞（HCT116）的体外抗肿瘤活性. 结果表明，大部分化合物具有一定的肿瘤抑制活性. 尤其是2-[5-硝基-2-（6-氯-2-苯甲酰基-1H-吲哚-3-胺基）嘧啶-4-胺基]乙酸乙酯（8j）对HCT116、MD-MBA-231的体外肿瘤抑制活性比阳性对照药品5-氟尿嘧啶分别高出2.0、0.5倍，体现出了较好的进一步研究价值.
黎秋 , 汪雨 , 胡孟金 , 陈鹏 , 游文玮 , 赵培亮 . 含吲哚环2,4-二氨基嘧啶类化合物的合成及抗肿瘤活性[J]. 有机化学, 2017 , 37(4) : 967 -974 . DOI: 10.6023/cjoc201611006
Based on our previous work, twenty-three novel 2,4-diaminopyrimidine derivatives bearing indole moiety were designed and synthesized. Structures of all compounds were elucidated by 1H NMR, 13C NMR and HRMS. Antiproliferative activities for all these compounds were evaluated by the method of methyl thiazolyl tetrazolium (MTT) assay against four cancer cell lines (HeLa, MD-MBA-231, PC-3 and HCT116), and the results demonstrated that some compounds possessed significant antitumor activities in vitro. Particularly, the most promising ethyl (2-((2-benzoyl-5-chloro-1H-indol-3-yl)amino)- 5-nitropyrimidin-4-yl)glycinate (8j) displayed 2.0- and 0.5-fold improvement compared to fluorouracil in inhibiting HCT116, and MD-MBA-231 cell proliferation with IC50 values of 23.15 and 36.88 mmol/L, respectively. These findings suggest that compound 8j may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
Key words： indole; pyrimidine; synthesis; antiproliferative activity
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