柠檬醛基抗油茶炭疽病菌衍生物的定量构效关系研究

Quantitative Structure-activity Relationship Analysis of Citral-based Antifungal Derivatives Against Colletotrichum gloeosporioides

为探讨柠檬醛基衍生物的结构与其对油茶炭疽病菌的抗菌活性之间的关系,研究了柠檬醛基抗油茶炭疽病菌衍生物的定量构效关系。使用计算化学软件Gauss View05、Gaussian 09W、Ampac和Codessa分别完成了柠檬醛基衍生物分子结构的构建、优化、描述符计算与筛选,以及QSAR模型建立。结果表明:建立了一个含有4个描述符:氢原子之间的相互斥力、分子中带正电荷加权部分表面积比例、氢原子的数量、分子表面正电荷分布以及分子总表面积的最佳QSAR模型,相关系数(R2)为0.926 5。对最佳QSAR模型进行内部检验和外部检验,其中留一法内部检验的RCV2=0.865 7,三重内部检验的Rtraining2=0.879 3、Rtest2=0.882 4;外部检验的R外2=0.946 7,表明该模型具有良好的稳定性和预测能力。解析建模描述符可知,柠檬醛基衍生物分子结构中与氢键供体相关的描述符对抗菌活性具有显著影响。本研究可为新型柠檬醛抗油茶炭疽病菌衍生物的设计与合成提供理论指导。

In order to investigate the relationship between the structure of citral derivatives and their antifungal activities against Colletotrichum gloeosporioides, the quantitative structure-activity relationship study of citral-based derivatives against C. gloeosporioides was carried out. The computational chemistry softwares GaussV iew 05,Gaussian 09 W,Ampac and Codessa were used to finish the molecular structure optimization,descriptor calculation and screening,and QSAR model construction.The results showed that the best QSAR model with four descriptors,including Min e-e repulsion for a H atom;ESP-FPSA-3 Fractional PPSA( PPSA-3/TMSA);number of H atoms;WPSA-3 Weighted PPSA( PPSA-3*TMSA/1000),were established,and its correlation coefficient( R2) was 0. 926 5. Internal validation and external validation of the best QSAR model were carried out. The result of the leave-one-out internal validation was RCV2= 0. 865 7,the results of the three-fold internal validation were Rtraining2= 0. 879 3,Rtest2= 0. 882 4,and the result of external validation was Rext2= 0. 946 7. These results indicated that the best QSAR model exhibited good stability and predictability. Analysis of the modeling descriptors indicated that the descriptors related to hydrogen bond donors in the molecular structure of citral-based derivatives had a significant effect on antifungal activity againstC. gloeosporioides. This study can provide theoretical guidance for the design of citral-based derivatives with better antifungal activity against C. gloeosporioides.