家蝇与大鼠GABA受体抑制剂的药效团模型及其3D-QSAR研究  

Pharmacophore Models and 3D-QSAR Studies of Rat and Fly′s GABA Receptor Inhibitors

作　　者：任天瑞[1] 沈斌[1,3] 裴剑锋[2] 汪永生[1] 向文胜[1] 

机构地区：[1]国家生物化学工程技术研究中心,中国科学院过程工程研究所 [2]北京大学化学与分子工程学院分子动态与稳态结构国家重点实验室,北京大学理论生物学中心 [3]中国科学院计算机网络信息中心,北京100080

出　　处：《高等学校化学学报》2005年第3期546-549,共4页Chemical Journal of Chinese Universities

基　　金：国家"九七三"计划项目 (批准号 :2 0 0 3 CB114 40 0 );国家"八六三"计划项目 (批准号 :2 0 0 3 AA2 3 5 0 10 -0 5 )资助 .

摘　　要：采用 DISCOtech方法 ,用 7个大鼠 γ-氨基丁酸 (GABA) A 受体抑制剂和 1 1个家蝇 GABAA 受体抑制剂分别建立了其药效团模型 ;用 Co MFA方法建立了 2 2个大鼠 GABAA 受体抑制剂和 2 9个家蝇 GABAA 受体抑制剂的 3 D-QSAR模型 ,模型的交叉验证相关系数分别为 0 .5 2 6和 0 .679,验证了药效团模型的合理性 。Aminobutyric acid(GABA) plays an important role as a major inhibitory neurotransmitter in both vertebrates and invertebrates, which have similar but pharmacologically distinct GABA_A receptors, so insects′ GABA_A receptors are regarded as a promising target for insecticides. In this paper, two pharmacophore models of rat and fly′s GABA_A receptors for a series of reported inhibitors were studied by DISCOtech methodology, which laid a foundation for finding the leading compounds and designing new selective compounds. According to this study, the three-dimensional quantitative structure and activity relationships were studied, which gave two predictive CoMFA models with q2__ rat= 0.526 and q2__ fly=0.679. The CoMFA models verified the pharmacophore models, and gave insights to the design of better GABA_A receptor inhibitors.

关 键 词：GABAA受体 药效团模型 三维定量构效关系(3D-QSAR) 比较分子力场分析(CoMFA) 

分 类 号：O641[理学—物理化学]