摘要
通过比较分子力场分析方法(Co MFA)研究取代喹啉类化合物对金黄色葡萄球菌抑菌活性(p M)的三维定量结构-活性相关(3D-QSAR)。12个化合物建立了预测模型,7个化合物作为验证集(含模板分子)。训练集的Co MFA模型显示立体场、静电场对生物活性贡献依次为49.8%、50.2%。该模型的交叉验证相关系数R2cv=0.650,非交叉验证相关系数R2=0.918,对测试集中的7个化合物的生物活性进行了预测,显示出较强的稳定性和良好的预测能力。通过分析Co MFA三维等势图发现,在取代喹啉类化合物抑菌机理中,R4取代基的强吸电性起主要作用,其次是其他取代基的疏水性作用。应用上述规律进行分子设计,获得了3个在理论上具有较高抑菌活性的新的取代喹啉衍生物,期待实验的验证。
The antibacterial activity( p M) of substituted quinolines against S. aureus were applied to 3D-QSAR analyses using the comparative molecular field analysis( Co MFA) method. 12 compounds were served to establish the predicting model,which were validated by evaluation of the test set of 7 compounds containing template molecule.The results based on the Co MFA model of training set showed that the contributions of steric and electrostatic fields to the bioactivity were 49. 8% and 50. 2%,respectively. The coefficients of cross-validation( R2cv),non crossvalidation( R2) for the model were 0. 650,0. 918,respectively,which were used to predict the activities of the training set and 7 analogues in the testing set. The results indicated that the model had strong stability and good predictability. The 3D contour maps suggested that the electron withdrawing groups on R4 have greater impact on antibacterial mechanism,followed by the hydrophobic factor of other substituents. Based on the above conclusions,three new molecules of substituted quinoline derivative with higher antibacterial activity had been theoretically designed and they were waiting for experimental verification.
出处
《化学通报》
CAS
CSCD
北大核心
2015年第2期153-157,共5页
Chemistry
基金
国家自然科学基金项目(21075138)
环境模拟与污染控制国家重点联合实验室开放基金项目(13K02ESPCT)
徐州市科技局基金项目(XM13B111)资助
关键词
取代喹啉
抑菌活性
比较分子场分析(CoMFA)
抑菌机理
分子设计
Substituted quinoline
Antibacterial activity
Comparative molecular field analysis(CoMFA)
Antibacterial mechanism
Molecular design
