Citation: Jian-Bo TONG, Xue-Chun XIAO, Ding LUO, Hai-Yin XU, Jie WANG. QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors[J]. Chinese Journal of Structural Chemistry, ;2021, 40(12): 1586-1594. doi: 10.14102/j.cnki.0254-5861.2011-3227 shu

QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors

Jian-Bo TONG ^{a, b,,} ,
Xue-Chun XIAO ^{a, b} ,
Ding LUO ^{a, b} ,
Hai-Yin XU ^{a, b} ,
Jie WANG ^{a, b}

a.
College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
b.
Shaanxi Key Laboratory of Chemical Additives for Industry, Xi'an 710021, China

Corresponding author: Jian-Bo TONG, jianbotong@aliyun.com
Received Date: 21 April 2021
Accepted Date: 15 June 2021

Figures(6)

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.
- Topomer CoMFA,
- HQSAR,
- molecular docking,
- isoquinolone derivatives,
- molecular design
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