6-氟-4-氧-1,4-二氢喹啉-3-羧基衍生物抗菌活性的QSAR研究

QSAR study on 6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives against Mycobacteria

为设计合成生物活性更高的喹诺酮类化合物,计算了可能会影响6-氟-4-氧-1,4二氢喹啉-3-羧基衍生物抗菌活性的最高占据轨道能级、最低空轨道能级、摩尔折射率、疏水参数等24个结构和量子化学参数,采用偏最小二乘、穷举回归和混沌遗传神经网络法对化合物的抗菌活性进行了定量结构活性关系(QSAR)研究,进而讨论了这些参数对抗菌活性的影响。结果表明:当该类化合物的生成热和极化率较大,最高占据轨道能、分子表面积、水合能和标准吉布斯自由能较小时对提高化合物抗菌活性有利。该QSAR的结果可为实验工作者合成新药提供理论参考。

The 6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives are calculated to guide the design and synthesis of the higher biological activity of quinolone compounds.Quantitative structure-activity relationship study has been approached on the basis of 24 structure and quantum chemical parameters including HOMO energy,LUMO energy,molar refractivity,hydrophobic parameters and so on,by using partial least squares,exhaustion regression and chaotic genetic artificial neural network.The results show that the antimycobacterial activity of quinolone compounds will increase when these compounds have larger heat of formation,ploarizability and/or lower HOMO energy,surface area,hydration energy and standard Gibbs free energy.The QSAR results can offer a theoretical reference for the pharmaceutical synthesis.