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化学进展 2009, Vol. 21 Issue (01): 66-76 前一篇   后一篇

• 中药研究专刊 •

五味子联苯环辛烯类木脂素成分的结构与药理活性关系和药物创新

余凌虹;刘耕陶*   

  1. (中国医学科学院和北京协和医学院药物研究所 北京 100050)
  • 收稿日期:2008-10-21 修回日期:1900-01-01 出版日期:2009-01-24 发布日期:2009-01-25
  • 通讯作者: 刘耕陶 E-mail:liugt@imm.ac.cn
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The Structure-Activity Relationship of Dibenzo (a,c) cyclooctene Lignans Isolated from Fructus schizandrae and Innovation of Novel Anti-Hepatitis Drugs

Yu Linghong;Liu Gengtao*   

  1. (Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China)
  • Received:2008-10-21 Revised:1900-01-01 Online:2009-01-24 Published:2009-01-25
  • Contact: Liu Gengtao E-mail:liugt@imm.ac.cn

传统中药五味子具有多种药理活性。20世纪70年代以来，我国临床发现五味子能改善慢性肝炎病人的肝功能异常，在此基础上，我所化学家和药理学家对五味子分离得到的20余种联苯环辛烯类木酯素成分和其药理作用进行了大量研究。五味子的药理活性主要有:保肝，抗氧化，诱导肝药酶，增强解毒功能，促进蛋白质、糖原合成，克服肿瘤耐药性,增强对抗药癌的敏感性以及对中枢神经系统的镇静作用。在这些研究基础上，合成了保肝作用最强的五味子丙素结构类似物，相继研制出两种抗肝炎新药联苯双酯（DDB）和双环醇（bicyclol）。本文对五味子木脂素类成分的结构与药理活性关系以及两种新药的创制做一综述。

关键词： 五味子, 联苯环辛烯类木脂素, 肝损伤, 肝炎, 双环醇, 抗氧化应激

Fructus schizandrae (FS) has been used as a corroborative for about two thousands of years in traditional Chinese medicines. In the early 1970’s, Chinese clinicians found that the whole powder and the honey pill of FS improved the abnormal liver function of chronic viral hepatitis. Following this clinical lead, the chemistry and pharmacology of FS are systematically studied in author's institute. Twenty dibenzo (a, c) cyclooctene lignans are isolated from different species of FS. The lignans have multiple pharmacological actions, mainly against liver injury, antioxidant, enhancing detoxification function, stimulating protein and glycogen biosynthesis, overcome multidrug resistance of cancer cells to chemotherapy as well as sedation on the central nervous system. Based on the study of the pharmacology and chemistry of FS, two novel anti-hepatitis drugs (DDB and bicyclol) are sequentially created through synthesizing analogues of schizandrin C, the most effective component of FS in anti-liver injury. The pharmacological action of different lignans and the relationship between structure and activity are reviewed in this paper.

Contents
1 Introduction
2 Chemical constituents of Fructus schizandrae (FS)
3 The structure-activity relationship of dibenzo (a,c) cyclooctene Lignans isolated from FS
3.1 Protective action of dibenzocyclooctene lignans isolated from schizandrae against liver injury and its mechanism
3.2 Antioxidant activity of the dibenzocyclooctene lignans isolated from FS
3.3 Protective effect of Sal on ox-LDL induced bovine aortic endothelium damage and oxidative stress induced neurotoxicity
3.4 Enhancing liver detoxification function—induction of the hepatic microsomal cytochrome P450
3.5 Stimulation of protein biosynthesis and glycogenesis in liver
3.6 Inhibitory effect on the central nervous system
3.7 Reversal multi-drug resistance to anti-cancer drugs
3.8 Summary
4 Synthesis of dibenzo (a,c) cyclooctene lignans and derivatives and innovation of novel anti-hepatitis drug
4.1 Innovation of novel DDB as anti-hepatitis drug
4.2 Innovation of second generative anti-hepatitis drug-bicyclol
5 Perspective

Key words: Fructus schizandrae, dibenzo (a,c)cyclooctene lignans, liver injury, hepatitis, bicyclol, anti-oxidative stress

中图分类号: 

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