摘要
基于比较分子力场分析(CoMFA)方法建立25种噻吩并嘧啶衍生物抗胃癌活性(pM)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(含模板分子)作为模型验证.已建立的CoMFA模型的交叉验证系数(R_(cv)^(2))、非交叉验证系数(R^(2))分别为0.369、0.831,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40.9%、59.1%,表明影响抗胃癌活性(pM)的主要因素是取代基的库仑力、氢键及配位,其次是取代基的疏水性和空间位阻.基于此研究结果,设计了4个具有较高抗胃癌活性的新化合物,有待医学实验验证.
Based on the comparative molecular field analysis(CoMFA) method,three dimensional quantitative structure-activity relationships(3 D-QSAR) between the molecular structures and their anti-gastric cancer activity(pM) of 25 thienopyrimidine derivatives were established. Twenty compounds in the training set were served to build the predicting models,and the six compounds(containing template molecule) in the test set were used to validate the models. The coefficients of the cross-validation(R_(cv)^(2)) and non cross-validation(R^(2)) for CoMFA model established in this study are 0. 369 and 0. 831,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 40. 9% and 59. 1%,respectively,indicating that the main factors to impact on p M are the Coulomb force,hydrogen bonds and coordination of substituted groups,followed by hydrophobic factor and steric hindrance of substituted groups. Base on the results and discussion,we also designed four novel molecules with satisfied predictions activity for the further experimental validation.
作者
唐自强
冯惠
冯长君
TANG Zi-Qiang;FENG Hui;FENG Chang-Jun(School of Material and Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China;Xuzhou Technical Institute,Xuzhou 221151,China)
出处
《原子与分子物理学报》
CAS
北大核心
2021年第3期35-40,共6页
Journal of Atomic and Molecular Physics
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(2016028)。
关键词
噻吩并嘧啶衍生物
抗胃癌活性
比较分子力场分析
分子设计
Thienopyrimidine derivative
Anti-gastric cancer activity
Comparative molecular field analysis
Molecular design
