文献类型：期刊文献

英文题名：Discovery of Two GSK3β Inhibitors from Sophora flavescens Ait. using Structure-based Virtual Screening and Bioactivity Evaluation

作者：Pan, Dabo[1,2];Zeng, Yong[3];Jiang, Dewen[1];Zhang, Yonghao[1];Wu, Mingkai[1];Huang, Yaxuan[1];Han, Minzhen[2];Jin, Xiaojie[4]

第一作者：Pan, Dabo

通信作者：Pan, DB[1];Pan, DB[2];Jin, XJ[3]

机构：[1]Qiandongnan Vocat & Tech Coll Nationalities, Dept Med Technol, Kaili 556000, Peoples R China;[2]Guizhou Med Univ, Affiliated Hosp 2, Dept Pharm, Kaili 556000, Peoples R China;[3]Chongqing Med Univ, Coll Pharm, Affiliated Dazus Hosp, Dazu 402360, Peoples R China;[4]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China

第一机构：Qiandongnan Vocat & Tech Coll Nationalities, Dept Med Technol, Kaili 556000, Peoples R China

通信机构：[1]corresponding author), Qiandongnan Vocat & Tech Coll Nationalities, Dept Med Technol, Kaili 556000, Peoples R China;[2]corresponding author), Guizhou Med Univ, Affiliated Hosp 2, Dept Pharm, Kaili 556000, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China.|[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;[10735]甘肃中医药大学;

年份：2024

外文期刊名：CURRENT COMPUTER-AIDED DRUG DESIGN

收录：;EI(收录号：20251718281259);WOS:【SCI-EXPANDED(收录号:WOS:001344792900001)】；

基金：This work was supported by the Project of National Natural Science Foundation of China (81803347), the Scientific and Technological Founding of Guizhou Province(QKHZC[2020]4Y087 and QKHZC[2022]YB289), University Science and Technology Innovation Team of Department of Education of Guizhou Province(QJJ[2023]099), the Scientific and Technological Founding of Qiandongnan(QDNKHJC[2023]10), and High-level Innovative Talents Program of Guizhou Province (QQCC[2022]201708).

语种：英文

外文关键词：GSK3 beta; Kushen; kushenol I; kushenol F; structure-based virtual screening

摘要：Objective Kushen (Sophora flavescens Ait.) has a long history of medicinal use in China due to its medicinal values, such as antibacterial, antiviral, and anti-inflammatory. Rapid discovery of the components and the medicinal effects exerted by Kushen will help elucidate the science of Kushen in curing diseases. GSK3 beta (glycogen synthase kinase-3 beta) is a protein kinase with a wide range of physiological functions, such as antibacterial, antiviral, and anti-inflammatory. The discovery of inhibitors targeting GSK3 beta from Kushen was not only helpful for the rapid discovery of the components responsible for the efficacy of Kushen but also important for the development of novel drugs.Methods In this study, the chemical composition of Kushen was extracted from the TMSCP database. Molecular docking, GSK3 beta enzyme assay, and molecular dynamics simulations were used to discover the GSK3 beta inhibitors from the chemical composition of Kushen.Results A total of 113 chemical compositions of Kushen were extracted from the TMSCP database. Molecular docking indicated that 15 chemical compositions of Kushen scored better than -8 kcal/mol against GSK3 beta. GSK3 beta enzyme assay demonstrated several inhibitory activities of kushenol I and kushenol F with IC50 values of 7.53 +/- 2.55 mu M and 4.96 +/- 1.29 mu M, respectively. Molecular dynamics simulations were used to reveal the interactions of kushenol I and kushenol F with GSK3 beta from structural and energetic perspectives.Conclusion Kushenol I and kushenol F could be the material basis for the antibacterial, antiviral, and anti-inflammatory properties of Kushen.