Design, Bio‐evaluation and Molecular Dynamics Simulation of Novel GSK‐3β Inhibitors. Issue 12 (29th July 2021)

• Record Type: Journal Article
• Authors: Lyu, Weiping; Li, Qihang; Li, Qi; Chen, Ying; Wang, Yingming; Tang, Tongzhong; Feng, Feng; Chi, Heng; Li, Yuan; Liu, Wenyuan; Sun, Haopeng
• Is Part Of: Molecular informatics. Volume 40:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-29
• Subjects: GSK-3β inhibitor -- Alzheimer's disease -- Virtual screening -- Lead compound; Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.202060031
• Languages: English
• ISSNs: 1868-1743

Abstract

Abstract: Glycogen synthase kinase 3 beta (GSK‐3β) is considered as a promising drug target for the treatment of Alzheimer's disease (AD). In the present study, two compound libraries were selected for virtual screening based on pharmacophore models of GSK‐3β to discover new inhibitors. Nine potential hits were retained for biological investigation and four of these compounds showed GSK‐3β inhibitory activity (with the IC50 values in sub‐micromolar range on GSK‐3β). Compounds 6 and 9 have good safety. They do not have any significant in vitro cytotoxicity against PC12 and SH‐SY5Y neuroblastoma cells at concentrations up to 90 μM. Based on the inhibitory activity and druggability properties, compound 8 is the preferred molecule, and it is a promising lead for the development of the GSK‐3β inhibitors for reducing the abnormal hyperphosphorylation of tau protein and relieving AD. Abstract :