对羟基苯甲酸酯类化合物抗菌活性的定量构效关系探讨

A QSAR Study on Antibacterial Activity of P-hydroxybenzoate Esters

摘要:

基于定量结构-活性关系（QSAR）研究对羟基苯甲酸酯类化合物性质具有重要意义。本文采用量子化学密度泛函理论（DFT）和逐步回归分析法研究了具有抗菌活性的11种对羟基苯甲酸酯类化合物的定量构效关系。在B3LYP/6-31G*水平上计算了对羟基苯甲酸酯类化合物的相关量子化学参数，得到在最稳定构型下分子结构参数，通过多元逐步回归分析筛选出对羟基苯甲酸酯类化合物影响抗大肠杆菌活性的主要因素并建立定量构效关系方程，采用留一法分析模型的稳定性及预测能力。结果表明对羟基苯甲酸酯类化合物抗大肠杆菌活性与最低空轨道能量（ELUMO）及偶极距（μ）呈正相关关系，QSAR模型表明化合物的最低空轨道能量、偶极距和极化率是影响对羟基苯甲酸酯类化合物抗菌活性的主要因素，ELUMO和μ越大，抗菌活性越大，所得QSAR模型对该类化合物抗菌活性有较好的预测效果。

Abstract:

The molecular structures of eleven kinds of p-hydroxybenzoate esters were optimized by using density functional theory (DFT) B3LYP method of quantum chemistry, and the quantitative structure-activity relationship (QSAR) of these compounds was studied. Stepwise multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The results suggested that ELUMO and had positive correlation on the activities of p-hydroxybenzoate esters, with correlation coefficient of 0.9910. The results showed that the lowest unoccupied molecular orbit ELUMO and the increase of dipole moment were the main independent factors contributing to the antifungal activity of the compounds. The antifungal activity increased with the increase of ELUMO and . The obtained QSAR model could provide theory reference to design p-hydroxybenzoate esters with stronger antibacterial activity.