摘要
基于分子拓扑邻接矩阵,计算了18种苯甲酰硫脲衍生物的原子类型电性拓扑状态指数(En)。通过多元线性逐步回归方法,建立了令人满意的En与苯甲酰硫脲衍生物对金黄色葡萄球菌的抑制活性(D)的定量结构-活性相关模型(QSAR)。该模型的相关系数(R2)、标准偏差(S)分别为0.861及1.273,该模型的计算值与相应实验值基本吻合。经Rcv2、VIF、FIT、AIC等指标检验,所建模型具有良好的预测能力与稳健性。利用该模型探讨了苯甲酰硫脲衍生物对金黄色葡萄球菌的抑制机理。根据进入模型的2个电性拓扑状态指数E1、E7可知,影响苯甲酰硫脲衍生物对金黄色葡萄球菌的抑制活性的主要因素是分子的二维结构特征-CH3和在芳环中=CH-等结构碎片。由结构修饰提出5种化合物,其中3种的抑菌活性均超出18mm,有待以后生物实验予以证实。
Kier＇s electrotopological state indices（ En） of atom types of 18 benzoyl thiourea derivative molecules are calculated based on the adjacency matrix of molecular topology in this paper. A satisfactory quantitative structure-activity relationship（ QSAR） between Enand inhibition activities（ D） to staphylococcus aureus of above compounds has been developed by using multiple linear stepwise regression. The correlation coefficient（ R2） and the standard deviation（ s） of the model were 0. 861 and 1. 273,respectively. Using Rcv2,VIF,FIT,AICtests,the model possessed better predictability and robustness. The calculated values were in good agreement with experimental data. The mechanism of the inhibition was also investigated. From the two parameters the eletrotopological state indices E1 and E7of the model,it is known that the dominant influence factors of bacteriostatic activity to staphylococcus aureus are the molecular structure fragments：-CH3 and = CH-in aromatics. According to the results（ 5 compounds） obtained from the structural modifications,the inhibition activities（ D） of three modified molecules is over 18 mm,and it is expected to be confirmed by using biologic experiments.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2015年第11期1693-1697,共5页
Chemical Research and Application
基金
国家自然科学基金(21075138)
环境模拟与污染控制国家重点联合实验室开放基金(13K02ESPCT)
徐州市科技局基金(XM13B111)
