喹唑啉衍生物抗胃癌活性的CoMFA模型  

CoMFA Model of Anti-gastric Cancer Activity of Quinazoline Derivatives

作　　者：冯长君[1] FENG Changjun(School of Material & Chemical Engineering, Xuzhou University of Technology, Xuzhou 221018, China)

机构地区：[1]徐州工程学院材料与化学工程学院,江苏徐州221018

出　　处：《徐州工程学院学报（自然科学版）》2022年第1期31-35,共5页Journal of Xuzhou Institute of Technology(Natural Sciences Edition)

基　　金：国家自然科学基金项目(21075138);结构化学国家重点实验室开放基金项目(2016028)。

摘　　要：基于比较分子力场分析(CoMFA)方法建立23种喹唑啉衍生物抗胃癌活性(pM_(G))的三维定量构效关系(3D-QSAR).训练集中20个化合物用于建立预测模型,测试集6个化合物(含16号模板分子及2个新设计的分子)作为模型验证.建立的CoMFA模型的交叉验证系数(Q^(2))、非交叉验证系数(R^(2))分别为0.312、0.854,说明所建模型具有较强的稳定性和良好的预测能力.该模型中立体场、静电场贡献率依次为62.6%、37.4%,表明影响抗胃癌活性(pM_(G))的主要因素是取代基的疏水性和空间位阻,其次是取代基的库仑力、氢键及配位.基于该研究结果,设计了2个具有较高抗胃癌活性的新化合物.Based on the comparative molecular field analysis(CoMFA)method,three dimensional quantitative structure-activity relationships(3D-QSAR)between the molecular structures and their anti-gastric cancer activity(pM_(G))of 23 quinazoline derivatives were established.Twenty compounds in the training set were served to build the predicting models,and the six compounds(containing template molecule 16 and newly designed two molecules)in the test set were used to validate the models.The coefficients of the cross-validation(Q^(2))and non-cross-validation(R^(2))for CoMFA model established in this study are 0.312 and 0.854,respectively.The results show that the model has strong stability and good predictability.In this model,the contributions of the steric and electrostatic fields were 62.6%and 37.4%,respectively,indicating that the main factors to impact on pM_(G) are the hydrophobic factor and steric hindrance of substituted groups,followed by Coulomb force,hydrogen bonds and coordination of substituted groups.Based on the results of this study,two new compounds with high anti-gastric cancer activity were designed.

关 键 词：喹唑啉衍生物 抗胃癌活性 比较分子力场分析 分子设计 

分 类 号：X171.5[环境科学与工程—环境科学] O6-051[理学—化学]