QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors
异喹诺酮衍生物 JNK1 抑制剂的 QSAR 研究和分子设计
イソキノリン誘導体JNK1阻害剤のQSAR研究と分子設計
QSAR 연구 및 이소퀴놀론 유도체 JNK1 억제제의 분자 설계
Estudio QSAR y diseño molecular de inhibidores JNK1 derivados de isoquinolonas
Étude QSAR et conception moléculaire des inhibiteurs JNK1 dérivés d'isoquinolone
Исследование QSAR и молекулярный дизайн ингибиторов JNK1, производных изохинолона
TONG Jian-Bo 仝建波 ¹ ², XIAO Xue-Chun 肖雪纯 ¹ ², LUO Ding 罗钉 ¹ ², XU Hai-Yin 徐海音 ¹ ², WANG Jie 王杰 ¹ ²
¹ College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
中国 西安 陕西科技大学化学与化工学院
² Shaanxi Key Laboratory of Chemical Additives for Industry, Xi'an 710021, China
中国 西安 陕西省轻化工助剂重点实验室
Chinese Journal of Structural Chemistry, 3 December 2021
Abstract
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 (q2) is 0.696 (Topomer CoMFA) and 0.826 (HQSAR), and the non-cross validation correlation coefficient (r2) 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.
