五味子素类抑制HIV活性的三维定量构效关系研究  

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

作　　者：李伟[1] 易翔[2] 肖培根[3] 褚凤鸣[2] 郭彦伸[2] 乔延江 毕开顺[1] 郭宗儒[2] 

机构地区：[1]沈阳药科大学药学系,沈阳110015 [2]中国医学科学院药物研究所,北京100050 [3]中国医学科学院药用植物资源研究所,北京100094

出　　处：《化学学报》2002年第7期1311-1317,共7页Acta Chimica Sinica

摘　　要：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q2 为 0 .71,非交叉验证相关系数r2 =0 .99,标准偏差SE =0 0 5 1,F =10 0 0 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 。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.

关 键 词：抑制HIV活性 三维定量构效关系 五味子 木脂素联苯环辛二烯类化合物 联苯类化合物 中药 抗艾滋病药物 

分 类 号：TQ461[化学工程—制药化工]