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

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.