4-取代喹啉衍生物抗菌活性的定量构效关系研究与分子设计  

The Quantitative Structure-Activity Relationship Study on the Bactericidal Activity of 4-Substituted Quinolone Derivatives and Their Molecular Design

作　　者：陈艳[1] 王玮[2] 堵锡华[1] CHEN Yan;WANG Wei;DU Xi-hua(School of Chemistry and Chemical Engineering;Library, Xuzhou University of Technology, Xuzhou 221111, China)

机构地区：[1]徐州工程学院化学化工学院,中国徐州221111 [2]徐州工程学院图书馆,中国徐州221111

出　　处：《湖南师范大学自然科学学报》2018年第3期46-51,共6页Journal of Natural Science of Hunan Normal University

基　　金：国家自然科学基金资助项目(21472071)

摘　　要：为了研究4-取代喹啉衍生物对大肠肝菌的抗菌活性(I.I.)的定量构效关系,基于拓扑理论,计算了36种上述化合物的分子电性距离矢量(Mi).通过最佳变量子集回归的方法建立了其中33种化合物对大肠肝菌抗菌活性的三元(M_(59),M_(67),M_7)QSAR模型,该模型的相关系数(R)、判断系数(R^2)及逐一剔除法交叉验证系数(RCV2)分别为0.904,0.817和0.761.模型通过不同的方法检验具有良好的稳健性及预测能力.根据进入模型的3个变量可知,影响4-取代喹啉衍生物对大肠肝菌的抗菌活性(I.I.)的主要结构片段是—NH—(或—NH=),=O,N,—O—(或—S—)和CH_3—.由该结论设计出4种新化合物,抗菌活性均超过73.04%,有待以后生物实验予以验证.In order to study the quantitative structure-activity relationship（ QSAR） of the bactericidal activity for 4-substituted quinolone derivatives on Escherichia coli,the molecular electronegativity distance vector（ Mi） of36 title compounds were calculated by the topological method. The three-parameter（ M59,M67,M7） QSAR model for the bactericidal activity of 33 compounds was constructed by leaps-and-bounds regression（ LBR） approach. The traditional correlation coefficient（ R）,determination coefficient（ R^2） and the leave-one-out cross-validation（ LOOCV） correlation coefficient（ R^2 CV） were 0.904,0.817 and 0.761,respectively. The built QSAR model demonstrates both robustness and prediction capability by multiple test methods. From the parameters of the model,it was known that the dominant influence factors of the bactericidal activity are the molecular structure fragments：—NH—（ or —NH=）,=O, N,—O—（ or —S—） and CH_3—. According to our results obtained from the structural modifications,the bactericidal activity（ I. I.） of four newly modified molecules can be as high as 73.04%,which is expected to be confirmed by biologic experiments in the future.

关 键 词：4-取代喹啉衍生物 抗菌活性 分子电性距离矢量 定量结构活性相关 分子设计 

分 类 号：O626.32[理学—有机化学]