4-氨基-1-羟基-2-氧-1,8-萘啶-3-甲酰胺类化合物抑制HIV整合酶链转移活性的主要微观结构因素探究  

Primary Microstructural Factors Inhibiting HIV Integrase Strand Transfer Activity of 4-Amino-1-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide Compounds

作　　者：康家雄 李爱秀[2] 靳玉瑞[2] 肖泽云[3] KANG Jiaxiong;LI Aixiu;JIN Yurui;XIAO Zeyun(Department of Pharmacy,Sichuan Corps Hospital of PAP,Leshan 614000,China;Drug Design Laboratory of the Basic Courses Department,Logistics University of PAP,Tianjin 300309,China;Department of Military Medicine,College of Health Service,Logistics University of PAP,Tianjin 300309,China)

机构地区：[1]武警四川省总队医院药剂科,四川乐山614000 [2]武警后勤学院基础部药物设计实验室,天津300309 [3]武警后勤学院卫勤系军事药学教研室,天津300309

出　　处：《化学与生物工程》2023年第6期16-21,34,共7页Chemistry & Bioengineering

基　　金：国家自然科学基金项目(81241114,30472166),天津市科技攻关计划重点科技攻关专项基金资助项目(06YFGZSH07000),乐山市重点研究项目(20SZD086)。

摘　　要：以25个4-氨基-1-羟基-2-氧-1,8-萘啶-3-甲酰胺类化合物为研究对象,利用遗传函数逼近法(GFA)构建了10个二维定量构效关系(2D-QSAR)模型,从中选取最优模型并检验其预测可靠性,并分析4-氨基-1-羟基-2-氧-1,8-萘啶-3-甲酰胺类化合物抑制HIV整合酶链转移活性的主要微观结构因素。结果表明,最优2D-QSAR模型的R^(2)=0.7776、Q^(2)=0.6421、r^(2)=0.87、(r^(2)-r′02)/r^(2)=0.01、k′=0.97、r^(2)_(m)=0.58,具有较高的稳定性和外部预测能力;热力学描述符AlogP、电拓扑状态描述符ES_Sum_sssN、ES_Sum_ssCH 2和空间描述符Shadow_nu是影响4-氨基-1-羟基-2-氧-1,8-萘啶-3-甲酰胺类化合物抑制HIV整合酶链转移活性的主要微观结构因素,其中Shadow_nu是最重要的微观结构因素。Using 25 kinds of 4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide compounds as research objects,we constructed 10 two-dimensional quantitative structure-activity relationship(2D-QSAR)models via genetic function approximation(GFA).Moreover,we selected an optimum model from 10 models,validated its external predictability,and analyzed the primary microstructural factors inhibiting HIV integrase strand transfer(INST)activity.The results show that the optimum 2D-QSAR model is obtained with R^(2)=0.7776,Q^(2)=0.6421,r^(2)=0.87,(r^(2)-r′02)/r^(2)=0.01,k′=0.97,and r^(2)_(m)=0.58,indicating that the optimum model has high stability and external predictability.Primary microstructural factors inhibiting HIV INST activity of 4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide compounds are descriptors AlogP,ES_Sum_sssN,ES_Sum_ssCH 2,and Shadow_nu,in which Shadow_nu is the most important microstructural factor.

关 键 词：4-氨基-1-羟基-2-氧-1 8-萘啶-3-甲酰胺 整合酶链转移 抑制剂 遗传函数逼近法 二维定量构效关系 

分 类 号：O641[理学—物理化学] R914.5[理学—化学]