亚氨基哒嗪类衍生物对人与昆虫GABA受体的选择性研究  

Selectivity of Iminopyridazine Derivatives for GABA Receptors in Human Being and Insects

作　　者：陈佳丽 翟纳 陈达 王秀美[1,2] 田亚锋 郑小娇 刘根炎[1,2] CHEN Jiali;ZHAI Na;CHEN Da;WANG Xiumei;TIAN Yafeng;ZHENG Xiaojiao;LIU Genyan(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China;Key Laboratory of Green Chemieal Proeess(Wuhan Institute of Technology),Ministry of Edueation,Wuhan 430205,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430205 [2]绿色化工过程教育部重点实验室(武汉工程大学),湖北武汉430205

出　　处：《武汉工程大学学报》2019年第1期12-18,24,共8页Journal of Wuhan Institute of Technology

基　　金：国家自然科学基金(21807082);湖北省自然科学基金(2017CFB121);湖北省教育厅科学技术研究项目(Q20171503);武汉工程大学大学生校长基金(2018006)

摘　　要：通过同源模建的方法构建了三种昆虫(家蝇、褐飞虱和斜纹夜蛾)的离子型GABA受体模型和人的α1β2γ2 GABA受体模型,并经能量优化、动力学模拟和拉氏图分析验证了所建模型的稳定性与合理性。将GABA受体竞争性拮抗剂亚氨基哒嗪类衍生物分别与所构建模型进行分子对接研究其作用机理,结果表明,亚氨基哒嗪类衍生物在昆虫模型中的对接打分与生物活性测试结果基本吻合,其与三种昆虫GABA受体的结合模式较人的GABA受体具有差异性和选择性。从分子层面预测和解释了昆虫GABA受体竞争性拮抗剂的选择性作用机理,为研发高效、安全的新靶点杀虫剂提供了理论依据和新思路。The ionotropic GABA receptor(GABAR)models of three kinds of insects(Musca domestica,Laodelphax striatellus and Spodopteralitura)and theα1β2γ2 GABAR model for human being were constructedby homology modeling.The stability and rationality of these models were verified by energy optimization,dynamic simulation,and Ramachandran graph analysis.The docking mechanisms of iminopyridazinederivatives as competitive antagonists of GABARs into the constructed models were investigated.The resultsindicated that the docking scores of the iminopyridazines in GABAR models of the insects were generallyconsistent with their bioactivities,while the binding patterns of iminopyridazines in GABARs of human beingand insect were different.This study predicted and explained the selectivity of competitive antagonists of insectGABARs at the molecular level and the docking mechanism,providing the theoretical basis and new ideas forthe development of new target insecticides with high efficiency and safety.

关 键 词：GABA受体 竞争性拮抗剂 亚氨基哒嗪类衍生物 分子对接 选择性 

分 类 号：S482.3[农业科学—农药学]