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

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.