马来酰亚胺类GSK-3β抑制剂的QSAR研究及分子设计  

QSAR study and molecular design of maleimide GSK-3β inhibitors

作　　者：陈艳[1] 吴琼[1] 堵锡华[1] 王玮[2] CHEN Yan;WU Qiong;DU Xi-hua;WANG Wei(School of Chemistry and Chemical Engineering,Xuzhou University of Technology,Xuzhou 21111,China;Xuzhou University of Technology Library,Xuzhou 212111,China)

机构地区：[1]徐州工程学院化学化工学院,江苏徐州221111 [2]徐州工程学院图书馆,江苏徐州221111

出　　处：《分子科学学报》2020年第2期138-144,I0004,共8页Journal of Molecular Science

基　　金：国家自然科学基金资助项目(21472071).

摘　　要：为了研究马来酰亚胺类化合物抑制活性与分子结构的定量构效关系,在分子理论的基础上计算了67个马来酰亚胺类化合物的电性距离矢量,通过最佳变量子集回归的方法,建立了抑制活性的五元线性回归模型,模型的传统相关系数(R2)和交叉验证相关系数(RCV2)分别为0.864和0.825.该模型经过Jackknife法检验、交叉验证、F检验及外部检验法证明具有良好的稳健性和预测能力.根据进入模型的5个变量分析,影响马来酰亚胺类GSK-3β抑制剂抑制活性的主要结构基团是-NH-,=O(或-OH),≡CH,Cl-及-O-(或-S-).同时基于QSAR模型设计了6个抑制活性显著提高的马来酰亚胺类分子,并预测了它们的抑制活性.In order to study the quantitative structure-activity relationship between inhibitory activity and molecular structure of maleimides, the molecular electrical distance vector of 67 maleimides were calculated on the basis of molecular theory. The five-variable QSAR model of inhibitory activity(pIC50) for the compounds was constructed by using leaps-and-bounds regression method. The traditional correlation coefficient(R2) and crossvalidated coefficient(RCV2) of this model are 0.864 and 0.825, respectively, The results demonstrated that the model is robust and has good prediction ability by using Jackknife test method, cross validation, F test and external inspection method. According to the analysis of five variables entering the model, the main structural groups affecting the inhibitory activity of maleimide GSK-3β inhibitors are -NH-,=O(or-OH),≡CH,Cl- and -O-(or-S-). Based on the QSAR model, six maleimide molecules with significantly increased inhibitory activity were designed and their inhibitory activities were predicted.

关 键 词：马来酰亚胺类化合物 糖原合成激酶 抑制活性 构效关系 分子设计 

分 类 号：O626[理学—有机化学]