新型噻唑-2-乙胺类HAT抑制剂的QSAR研究  

QSAR study on novel HAT inhibitors of amide and urea derivatives of thiazol-2-ethylamines

作　　者：段家喜 赵赛 易忠胜[1,2,3] 聂瑾芳[1,2,3] DUAN Jia-xi;ZHAO Sai;YI Zhong-sheng;NIE Jin-fang(College of Chemistry and Bioengineering,,Guilin University of Technology,Guilin 541004,China;Guangxi College and Universy Key Laboratory of Food Safety and Detection,Guilin University of Technology,Guilin 541004,China;Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area,Guilin University of Technology,Guilin 541004,China)

机构地区：[1]桂林理工大学化学与生物工程学院,广西桂林541004 [2]桂林理工大学广西高校食品安全与检测重点实验室,广西桂林541004 [3]桂林理工大学岩溶地区水污染控制与用水安全保障协同创新中心,广西桂林541004

出　　处：《桂林理工大学学报》2018年第3期529-536,共8页Journal of Guilin University of Technology

基　　金：国家自然科学基金项目(21267008; 21467006);广西自然科学基金项目(2014GXNSFAA118034);广西高等学校高水平创新团队及卓越学者计划项目(桂教人[2014]49)

摘　　要：采用VSMVI变量筛选方法从大量描述符中筛选最优子集,再由MLR回归方法建立了83个噻唑-2-乙胺类化合物与非洲人类锥虫病(HAT)抑制活性之间的二维定量结构-活性相关(2D-QSAR)模型,最优模型的拟合相关系数(r^2=0. 889 2)和交叉验证相关系数(q^2=0. 857 4)表明模型具有良好的稳健性、拟合能力和预测能力。模型的描述符在一定程度上反映了分子的二维结构和疏水性对抑制活性具有重要影响。同时采用基于CoMFA和CoMSIA方法的三维定量结构-活性相关(3D-QSAR)建立了相关性显著、预测能力强的定量模型(CoMFA:r^2=0. 924,q^2=0. 516; CoMSIA:r^2=0. 944,q^2=0. 531),其中CoMSIA的疏水场贡献率最高,说明了分子的疏水作用对抑制活性的重要影响。2D-QSAR models are developed to predict the activity against trypanosoma brucei rhodesiense of amide and urea derivatives of thiazol-2-ethylamines.The VSMVI(variable selection method based on variable interaction)technique is used to select optimal subset from large-size molecular descriptors.Multiple linear regression(MLR)method is employed to construct the QSAR models.The correlation coefficient of leave-one-out cross validation(q 2=0.857 4)and fitting correlation coefficient of models(r 2=0.889 2)show that the model is robust and has good fitting and prediction for selecting bioactivities.The descriptor of the 2D-QSAR model reflects,to some extent,that the two-dimensional structure and hydrophobicity of the molecules play an important role on the inhibitory activity.Simultaneously,the models of three-dimensional quantitative structure-activity relationship(3D-QSAR)based on CoMFA and CoMSIA show a significant correlation and strong predictive ability(CoMFA:r 2=0.924,q 2=0.516.CoMSIA:r 2=0.944,q 2=0.531).The highest contribution rate of CoMSIA hydrophobic field indicates that the hydrophobic interaction of molecules has an important effect on the inhibitory activity.

关 键 词：噻唑-2-乙胺类化合物 非洲人类锥虫病(HAT) 二维定量结构-活性相关(2D-QSAR) 基于变量相互作用的变量筛选方法(VSMVI) 比较分子场分析方法(CoMFA) 比较分子相似性指数分析法(CoMSIA) 

分 类 号：R917[医药卫生—药物分析学]