脂肪酸及其衍生物对蜡样芽孢杆菌抑菌活性的定量构效关系

Quantitative Structure-Activity Relationships of Antimicrobial Fatty Acids and Derivatives Against Bacillus

测定了57种脂肪酸及其衍生物对蜡样芽孢杆菌的最低抑制浓度,并利用结构描述符回归法(SDQSAR)和比较分子立场分析法(Co MFA)研究脂肪酸衍生物的结构与抑菌活性之间的定量关系,获得了预测能力较优的两个模型(SDQSAR:R2=0.881,Q2LOO=0.832;Co MFA:R2=0.835,Q2LOO=0.523)。模型分析结果表明,影响脂肪酸抑菌活性的主要因素为立体效应和电性特征;原子排布较密,空间体积在一定范围,某些位置没有大的立体位阻,羧基、酯基端电负性强,特定的电子云排布和对外电场较敏感的脂肪酸分子更易具有较强抑菌能力。研究获得的QSAR模型可用于指导新型高效脂肪酸衍生物抑菌剂的设计,减小设计合成工作量,提高成功的可能性。

The MIC of 57 fatty acids and fatty acid derivatives against Bacillus were examined. SDQSAR（Structure Descriptors regression Quantitative Structure-Activity Relationship） and Co MFA（Comparative Molecular Field Analysis）were both performed and two statistically reliable models were established： SDQSAR： R^2=0.881, QLOO^2=0.832; CoMFA：R^2=0.835, QLOO^2=0.523, and better predictive power would be achieved by the combination of SDQSAR and Co MFA models. By interpreting these models we found that steric and electronic properties are the most related factors with inhibitory effect, and the fatty acid derivative molecules which possessed denser atomic distribution, space volume in certain range,no steric effect in some regions, more electronic negativity of carboxyl terminal of fatty acid chains, and special electron cloud distribution and particular sensitivity to outer electric field were tend to display more potent antimicrobial activity.Above all, some of the fatty acid derivatives such as monotridecanoin, gamma-linolenic acid and monoarachidonin were found to inhibit Bacillus potently for the first time, and these QSAR models could be useful in designing novel potent fatty acid derivatives as antimicrobial agents.