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

doi:10.6023/cjoc201907006

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

含吲哚的吡唑并[3,4-d]嘧啶衍生物的设计合成及其生物活性研究

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

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 E-mail:yalisong@hbu.edu.cn;xiaoqiao@hbu.edu.cn
基金资助:
河北省自然科学基金（No.B2018201269、河北省高等学校科学技术研究项目（No.ZD2019060）、国家自然科学基金（No.21675039）、河北省青年拔尖人才资助项目.

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

Sun Xiaoyang^a,b, Feng Siran^a, Dong Jinjiao^a, Feng Jiajia^a, Liu Zhenming^c, Song Yali^a, Qiao Xiaoqiang^a,d

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.

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Abstract

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

Cite this article

Sun Xiaoyang, Feng Siran, Dong Jinjiao, Feng Jiajia, Liu Zhenming, Song Yali, Qiao Xiaoqiang. Design, Synthesis and Biological Activity of Pyrazolo[3,4-d]pyrimidine Derivatives Containing Indole Moiety[J]. Chinese Journal of Organic Chemistry, 2020, 40(2): 391-397.

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含吲哚的吡唑并[3,4-d]嘧啶衍生物的设计合成及其生物活性研究

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

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