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2014 , Vol. 34 >Issue 6: 1167 - 1171

DOI: https://doi.org/10.6023/cjoc201312029

研究论文

鬼臼毒素五元氮杂环类衍生物的合成及细胞毒活性研究

  • 朱培芳 ,
  • 赵静峰 ,
  • 羊晓东 ,
  • 张洪彬
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  • a. 云南中医学院实验中心 昆明 650500;
    b. 云南大学教育部自然资源药物化学重点实验室 昆明 650091

收稿日期: 2013-12-24

  修回日期: 2014-01-27

  网络出版日期: 2014-02-14

基金资助

国家自然科学基金（Nos. 20702045，21072164）和云南省自然科学基金（Nos. 2013FA028，2012FB113）资助项目.

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Synthesis and Cytotoxic Activity of Podophyllotoxin Five-Membered N-Heterocyclic Derivatives

  • Zhu Peifang ,
  • Zhao Jingfeng ,
  • Yang Xiaodong ,
  • Zhang Hongbin
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  • a. Experimental Center, Yunnan University of Traditional Chinese Medicine, Kunming 650500;
    b. Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, Yunnan University, Kunming 650091

Received date: 2013-12-24

  Revised date: 2014-01-27

  Online published: 2014-02-14

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 20702045, 21072164) and the Natural Science Foundation of Yunnan Province (Nos. 2013FA028, 2012FB113).

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摘要

从鬼臼毒素出发，通过简洁的合成路线合成了9个新型的鬼臼毒素五元氮杂环类衍生物，其结构经1H NMR，13C NMR，IR，HR-ESI-MS以及X单晶衍射确定. 对合成的新化合物进行了体外抗肿瘤活性的筛选，结果表明，化合物10具有较好的细胞毒活性，IC50值为2.63～4.73 μmol/L，对4种细胞株的活性均优于顺铂，可以作为先导化合物作进一步的结构修饰和更深入的活性研究.

关键词： 鬼臼毒素; 五元氮杂环; 结构改造; 细胞毒活性

本文引用格式

朱培芳 , 赵静峰 , 羊晓东 , 张洪彬 . 鬼臼毒素五元氮杂环类衍生物的合成及细胞毒活性研究[J]. 有机化学, 2014 , 34(6) : 1167 -1171 . DOI: 10.6023/cjoc201312029

Abstract

Nine novel podophyllotoxin five-membered N-heterocyclic derivatives have been prepared from commercially podophyllotoxin. Their structures were confirmed by 1H NMR, 13C NMR, IR, HR-ESI-MS and X-ray crystallographic analysis. These derivatives have been evaluated in vitro against a panel of human tumor cell lines. Compound 10 (IC50: 2.63～4.73 μmol/L) showed superior cytotoxic activity compared with DDP (a clinically available anticancer drug) in four human tumor cell lines investigation, which is to be a lead compound for further structural modifications and activity research.

Key words： podophyllotoxin; five-membered N-heterocycles; structure modification; cytotoxic activity

参考文献

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[13] CCDC 977807 contains the supplementary crystallographic data for compound 10. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/ data_request/cif.
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