QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors  

作　　者：TONG Jian-Bo XIAO Xue-Chuna LUO Ding XU Hai-Yin WANG Jie 仝建波;肖雪纯;罗钉;徐海音;王杰(College of Chemistry and Chemical Engineering,Shaanxi University of Science and Technology,Xi'an 710021,China;Shaanxi Key Laboratory of Chemical Additives for Industry,Xi'an 710021,China)

机构地区：[1]College of Chemistry and Chemical Engineering,Shaanxi University of Science and Technology,Xi'an 710021,China [2]Shaanxi Key Laboratory of Chemical Additives for Industry,Xi'an 710021,China

出　　处：《Chinese Journal of Structural Chemistry》2021年第12期1586-1594,1551,共10页结构化学（英文）

基　　金：This work was supported by the National Natural Science Funds of China(21475081);Innovation Supporting Plan of Shaanxi Province-Innovation Research Team(No.2018TD-015);the Graduate Innovation Fund of Shaanxi University of Science and Technology.

摘　　要：JNK1 is a drug target for the treatment of type 2 diabetes,and it plays a key mediator role in metabolic disorders.In this paper,holographic quantitative structure-activity relationship(HQSAR)technology and Topomer comparative molecular field analysis(Topomer CoMFA)technology are used to analyze the quantitative structure-activity relationship(QSAR)of 39 isoquinolone derivatives.The cross validation correlation coefficient(q^(2))is 0.696(Topomer CoMFA)and 0.826(HQSAR),and the non-cross validation correlation coefficient(r^(2))is 0.935(Topomer CoMFA)and 0.987(HQSAR).The results showed that the models have good stability and predictive ability.The Topomer search module was applied to define high contribution fragments in the ZINC database,designing 20 new isoquinolone compounds with theoretically high inhibitory activity.The molecular docking was carried out to explore the interaction between the ligand and target JNK1 protein.This study can provide a theoretical basis for the design of new JNK1 inhibitors.

关 键 词：Topomer CoMFA HQSAR molecular docking isoquinolone derivatives molecular design 

分 类 号：TQ460.1[化学工程—制药化工]