高等学校化学学报

• 研究论文 • 上一篇    下一篇

GABAA受体萜类抑制剂构效关系研究

任天瑞1; 赵保峰1,2; 胡远东3; 次素琴1,2   

  1. 1. 生物化学工程国家重点实验室, 中国科学院过程工程研究所, 北京 100080;
    2. 中国科学院研究生院, 北京 100039;
    3. 军事医学科学院药物研究所, 北京 100850
  • 收稿日期:2005-06-22 修回日期:1900-01-01 出版日期:2006-07-10 发布日期:2006-07-10
  • 通讯作者: 任天瑞

Structure-activity Relationships of Inhibitor of Terpenoids in GABAA Receptor

REN Tian-Rui1*; ZHAO Bao-Feng1,2; HU Yuan-Dong3; CI Su-Qin1,2   

  1. 1. State Key Laboratory of Biochemical Engineering, Institute of Process
    Engineering, Chinese Academy of Sciences, Beijing 100080, China;
    2. The Graduate University of Chinese Academy of Sciences, Beijing 100039,
    China;
    3. Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
  • Received:2005-06-22 Revised:1900-01-01 Online:2006-07-10 Published:2006-07-10
  • Contact: REN Tian-Rui

摘要: 采用DISCOtech方法建立了大鼠和家蝇GABAA受体萜类抑制剂的药效团模型, 根据药效团模型叠加规则建立了大鼠和家蝇GABAA受体萜类抑制剂CoMFA模型, 模型的交叉验证相关系数分别为0.713和0.738. 构效关系研究显示, 家蝇和大鼠受体抑制剂结合部位之间存在一个主要差别: 与受体作用的抑制剂的负电荷基团取代有利于保持其对哺乳动物的高抑制活性, 而保持对昆虫的高抑制活性是不需要的, 从而为寻找先导化合物和设计高选择性杀虫剂提供了理论指导.

关键词: 萜类抑制剂, 杀虫剂, 药效团模型, GABAA受体, 比较分子力场分析(CoMFA)

Abstract: A variety of terpenoids of plant origin such as anisatin, picrotoxinin and picrodendrins were shown to be noncompetitive antagonists of GABAA receptors. The results show the selectivity toward the insect receptor and thus represent new leads toward selective insecticides. Two pharmacophore models of rat and housefly′s GABAA receptors for terpenoids inhibitors were studied by DISCOtech methodology. Two pharmacophore models were verified by the study of the threedimensional quantitative structure and activity relationships, which gave two predictive CoMFA models with q2rat=0.713 and q2fly=0.738. According to these results, it was found that negatively charged particle of inhibitor contributed strongly to binding at the rat receptor but showed almost no contribution to the housefly receptor. So these findings will lay a foundation of finding leading compounds and give some guidance on synthesizing insecticides with selectivity activity.

Key words: Inhibitors of terpenoids, Insecticide, Pharmacophore model, GABAA receptor, Comparative molecular field analysis

中图分类号: 

TrendMD: