Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (2): 391-397.DOI: 10.6023/cjoc201907006 Previous Articles     Next Articles


孙晓阳a,b, 冯思冉a, 董金娇a, 冯佳佳a, 刘振明c, 宋亚丽a, 乔晓强a,d   

  1. a 河北大学药学院 河北省药物质量分析控制重点实验室 河北保定 071000;
    b 沧州市中心医院 国家药物临床试验机构 河北沧州 061000;
    c 北京大学药学院 天然药物及仿生药物国家重点实验室药物设计中心 北京 100191;
    d 河北大学 药物化学与分子诊断教育部重点实验室 河北保定 071000
  • 收稿日期:2019-07-03 修回日期:2019-09-11 发布日期:2019-11-01
  • 通讯作者: 宋亚丽, 乔晓强;
  • 基金资助:

Design, Synthesis and Biological Activity of Pyrazolo[3,4-d]pyrimidine Derivatives Containing Indole Moiety

Sun Xiaoyanga,b, Feng Sirana, Dong Jinjiaoa, Feng Jiajiaa, Liu Zhenmingc, Song Yalia, Qiao Xiaoqianga,d   

  1. a Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacetical Sciences, Hebei University, Baoding, Hebei 071000;
    b National Drug Clinical Trial Institution, Cangzhou Central Hospital, Cangzhou, Hebei 061000;
    c Drug Design Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191;
    d Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, Hebei 071000
  • Received:2019-07-03 Revised:2019-09-11 Published:2019-11-01
  • Supported by:
    Project supported by the Natural Science Foundation of Hebei Province (No. B2018201269), the Research Award Fund Scientific and Technological in Higher Education Institutions of Hebei Province (No. ZD2019060), the National Natural Science Foundation of China (No. 21675039), and the Young Talent of Hebei Province.

Based on the combination principle in drug design, thirteen pyrazolo[3,4-d]pyrimidine derivatives containing indole moiety were designed and synthesized. The target compounds were confirmed by 1H NMR, 13C NMR and HRMS. Their in vitro cytotoxicity against four human cancer cell lines (HeLa、MGC-803、MCF-7、BEL-7404) has been investigated and most of the tested compounds displayed moderate antiproliferative activity. Especially, compound 5m exhibited the highest level of antiproliferative activity with an IC50 value <30 μmol·L-1 for HeLa, MGC-803 and MCF-7. IC50 value of methyl 3-((4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)thio)-1H-indole-6-carboxylate (5m) to MCF-7 was (4.02±0.92) μmol·L-1, which was better than etoposide (10.1±0.62 μmol·L-1) and camptothecin (5.93±0.56 μmol·L-1). Further biological evaluation of these compounds suggested that these compounds showed selective inhibitory activity against Topo II as a possible intracellular target, and all compounds didn't show inhibitory activity against Topo I.

Key words: indole, pyrazolo[3,4-d]pyrimidine, anticancer, topoisomerase, molecular docking