摘要
运用比较分子力场分析(CoMFA)方法,建立25种噻吩并吡啶并嘧啶衍生物分子结构与抗鼻咽鳞癌活性(pM)的三维定量构效关系(3D-QSAR),以揭示影响pM的微观结构因素,探讨其体外抗肿瘤作用的分子机理。训练集中20个化合物用于建立预测模型,测试集含13号模板分子和新设计的3个分子共9个化合物,用于模型验证。所建CoMFA模型的交叉验证系数R2cv、非交叉验证系数R2分别为0.372、0.853。该模型中立体场、静电场贡献率依次为53.7%、46.3%,表明影响pM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。设计了3个具有较高抗鼻咽鳞癌活性的新化合物,有待医学实验验证。
Based on the comparative molecular field analysis(CoMFA)method,three dimensional quantitative structure-activity relationships(3D-QSAR)between the molecular structures and their anti-tumor activity in nasopharyngeal squamous carcinoma(pM)of 25 thieno-pyrido-pyrimidine derivatives are established to reveal the micro factors affecting pM and explore the molecular mechanism of its anti-tumor effect in vitro.Twenty compounds in the training set are served to build a predicting model,and nine compounds in the test set are used to validate the model containing template molecule 13 and three novel molecules designed here.The coefficients of the cross-validation(R2cv)and non cross-validation(R2)for CoMFA model established here are 0.372 and 0.853,respectively.The contributions of the steric and electrostatic fields are 53.7%and 46.3%,respectively.It shows that the main factors affecting pM are the hydrophobic factor and steric hindrance of substituted groups,followed by Coulomb force,hydrogen bonds and coordination of substituted groups.Three new molecules with satisfied predictions activity are designed for the further experimental validation.
作者
秦正龙
杨伟华
冯长君
Qin Zhenglong;Yang Weihua;Feng Changjun(School of Chemistry and Materials Science,Jiangsu Normal University,Xuzhou 221116,China;School of Materials and Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China)
出处
《南京理工大学学报》
CAS
CSCD
北大核心
2021年第6期722-727,共6页
Journal of Nanjing University of Science and Technology
基金
国家自然科学基金(21075138)
结构化学国家重点实验室开放基金(20160028)。
关键词
噻吩并吡啶并嘧啶衍生物
鼻咽鳞癌
抗癌活性
比较分子力场分析
分子设计
立体场
静电场
thieno-pyrido-pyrimidine derivatives
nasopharyngeal squamous carcinoma
anti-tumor activity
comparative molecular field analysis
molecular design
steric fields
electrostatic fields
