乙酰胆碱酯酶抑制剂药效团模型的构建(英文)  

Construction of the pharmacophore model of acetylcholinesterase inhibitor

作　　者：祝勇[1] 童心玥[1] 赵玥[1] 陈卉[1] 姜凤超[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《药学学报》2008年第3期267-276,共10页Acta Pharmaceutica Sinica

摘　　要：利用CATALYST系统,由具有相同作用机制,不同结构特征的93个已知的乙酰胆碱酯酶抑制剂(AChEIs)构建出了含有3个疏水单元,1个环芳香性单元和1个氢键受体单元的药效团模型,优化的模型(RMS=0.53,correl=0.93,weight=3.29,config=19.05,total cost-null cost=62.75)可分别作用于乙酰胆碱酯酶的双活性作用部位,并能准确预测用于临床的阿尔茨海默病(AD)治疗的乙酰胆碱酶抑制剂的活性,有利于设计和改造具有新结构的用于AD治疗的乙酰胆碱酶抑制剂。Based on ninety three acetylcholinesterase inhibitors （AChEIs） which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed （Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05 ）. This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer＇ s disease （ AD）, and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer＇ s disease （AD） by virtual screening.

关 键 词：阿尔茨海默病 乙酰胆碱酯酶抑制剂 药效团模型 计算机辅助药物设计 双活性作用部位 

分 类 号：R916[医药卫生—药学]