取代喹啉类化合物抗菌活性的定量构效关系及分子设计

采用密度泛函理论(DFT)和逐步回归分析法对15种新合成的取代喹啉类化合物进行了定量构效关系(QSAR)研究. 在B3LYP/6-31G(d,p)水平上计算了取代喹啉的量子化学参数, 通过逐步多元回归分析筛选出影响抗菌活性的主要因素, 建立了定量构效关系方程, 并用留一法交叉分析了模型的稳定性及预测能力. 结果表明, C5的亲核电子密度fNC5及C9-N1的键级BC9-N1是影响喹啉类化合物抗金黄色葡萄球菌活性的主要因素, 所得模型对该类化合物抗菌活性有较好的预测效果. 同时基于QSAR研究结果设计了4个活性较高的新喹啉衍生物.

QSAR and Molecular Design of Some Quinoline Derivatives as Antimicrobial

The relationship between structures and antibacterial activities of 15 quinoline derivatives were studied by using both density functional theory (DFT) at the B3LYP/6-31G (d, p) basis set and stepwise multiple linear regression analysis (SMLR) method. The main independent factors which affected the activity of the compounds were determined by stepwise regression analysis, then a QSAR model was established. The stability and predictive ability of the model were examined by “leave-one-out”(LOO) cross-validation method. The result suggested that the nucleophilic frontier electron density of C(5) atom ( ), the bond order of C(9)-N(1) ( ) were the predominant factors affecting antibacterial activity against S. aureus. The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values were 0.814 and 0.734 respectively, showing this model with a good predictability. Based on this QSAR study, 4 new compounds with high antibacterial activity had been theoretically designed.