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化学学报
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化学学报 ›› 2002, Vol. 60 ›› Issue (7): 1311-1317. 上一篇    下一篇

研究论文

五味子素类抑制HIV活性的三维定量构效关系研究

李伟;易翔;肖培根;褚凤鸣;郭彦伸;乔延江;毕开顺;郭宗儒   

  1. 沈阳药科大学药学系,沈阳(110015);中国医学科学院药物研究所.北京 (100050);中国医学科学院药用植物资源研究所.北京(100094)
  • 发布日期:2002-07-15

3D-QSAR Study of schizandrins for Anti-HIV Using Comparative Molecular Similarity Indices Analysis

Li Wei;Yi Xiang;Xiao Peigen;Chu Fengming;Guo Yansheng;Qiao Yanjiang;Bi Kaishun;Guo Zongru   

  1. Shenyang Pharmaceutical University,Shenyang(110015);Institute of Materia Medica, Chinese Academy of Medical Sciences.Beijing(100050);Institute of Medical Plants Development, Chinese Academy of Medical Sciences.Beijing(100094)
  • Published:2002-07-15

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被引次数

48 | 4

建立了五味子活性成分木脂素类和联苯类化合物抑制HIV活性的三维定量构效 方程。采用联苯环原子和苯环质心两种叠合方式，并区分联苯化合物的不同构型， 共建立了四类CoMSIA模型，其中训练集中联苯类为S构型并叠合联苯环原子建立的 CoMSIA模型相关性最好，交叉验证相关系数q~2为0.71，非交叉验证相关系数r~2 = 0.99，标准偏差SE = 0.051, F = 1000.6。CoMSIA方法采用Gaussian函数计算 场能，并在CoMFA方法的立体和静电场基础上加入疏水场，PLS分析结果更为准确。 该模型三维等势图证实了某些结构和活性规律，如联苯基共面性越好，活性越高， 同时给出了苯环上取代基的体积、电性和疏水性要求，为该类化合物的结构改造提 供了依据。

关键词: 五味子, 木质素, 联苯 P, 环辛二烯, 定量构效关系

The present study constructs a model of three-dimensional quantitative structure and bioactivity of anti-HIV for a Chinese traditional medicine-Schizandrins, by implementing a new 3D-QSAR technique: comparative molecular similarity indices analysis (CoMSIA). Here four models are built based on different form of biphenyl and two aligned methods. The results of PLS analyses indicate that a good 3D- QSAR model can be obtained if biphenyl prefers S form and all the compounds are aligned according to the atoms in biphenyl group. After field expressions in terms of similarity indices in CoMSIA instead of the conventionally used Lennard-Jones and Coulomb-type potentials in CoMFA, the cross-validated q~2 and predictive ability are significantly improved. The CoMSIA coefficient contour plots identify several key features that the torsion angel of two benzene planes is a critical factor for the activity and the substituent at cyclooctadiene is also related to the activity, which are very valuable for designing and optimizing new active structures.

Key words: SCHISANDRA CHINENSIS, LIGNIN, DIPHENYL P, CYCLOOCTADIENE, QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP

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