培氟沙星均三唑硫醚类化合物抗增殖活性的3D-QSAR研究与分子设计  

3D-QSAR study and molecular design of anti-proliferative activity for pefloxacin isoriazole sulfide derivatives to human leukemia cells

作　　者：冯惠 王晓辉[1] 王菊[1] 冯长君[1] FENG Hui;WANG Xiao-hui;WANG Ju;FENG Chang-jun(School of Material and Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,Jiangsu,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：《云南大学学报（自然科学版）》2021年第1期142-146,共5页Journal of Yunnan University(Natural Sciences Edition)

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).

摘　　要：基于比较分子力场分析(CoMFA)方法建立24种培氟沙星均三唑硫醚衍生物对人白血病细胞(HL60)抗增殖活性(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10个化合物(含模板分子22及新设计的5个分子)作为模型验证.已建立的3D-QSAR模型的交叉验证系数(Rcv^2)、非交叉验证系数(R2)分别为0.436、0.903,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71.8%、28.2%,表明影响抗增殖活性(pM)的主要因素是在苯环的3,4-位上引入小体积的负电性基团.基于三维等势图,设计了5个具有较高抗增殖活性的分子,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 the in vitro antiproliferative activity(pM)of 24 pefloxacin isotriazole sulfide derivatives against Human leukemia cells(HL60)were established.Twenty compounds in the training set were served to build the predicting models,and the test set of ten compounds(containing template molecule 22 and newly designed 5 molecules)were used to validate the models.The coefficients of the cross-validation(Rcv^2)and non cross-validation(R2)for CoMFA model established in this study were 0.436 and 0.903,respectively.The results showed that the model had better statistical stability and predictive ability.In this model,the contributions of the steric and electrostatic fields were 71.8%and 28.2%,respectively,indicating that the main factor to impact on pM were the electronegative substituted groups of small volume was introduced at the 3,4-position of the benzene ring.Base on the CoMFA contour maps,we also designed five novel molecules with satisfied prediction activity for the further experimental validation.

关 键 词：培氟沙星均三唑硫醚衍生物 人白血病细胞 抗增殖活性 比较分子力场分析 分子设计 

分 类 号：R979[医药卫生—药品] R911[医药卫生—药学]