Citation: 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. doi: 10.6023/cjoc201907006 shu

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

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

Corresponding author: Song Yali, yalisong@hbu.edu.cn Qiao Xiaoqiang, xiaoqiao@hbu.edu.cn
Received Date: 3 July 2019
Revised Date: 11 September 2019
Available Online: 1 February 2019
Fund Project: 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

Figures(7)

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.
- indole,
- pyrazolo[3, 4-d]pyrimidine,
- anticancer,
- topoisomerase,
- molecular docking
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