Design, synthesis and biological evaluation of mogrol derivatives as a novel class of AMPKα2β1γ1 activators. Issue 2 (15th January 2020)

• Record Type: Journal Article
• Authors: Wang, Junwei; Liu, Junhua; Xie, Zhifu; Li, Jia; Li, Jingya; Hu, Lihong
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 2(2020)
• Publication Date: 2020-01-15
• Subjects: AMPK -- AMPKα2β1γ1 activators -- Mogrol derivatives -- Structure-activity relationships; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126790
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Adenosine monophosphate-activated protein kinase (AMPK) has been considered as a promising drug target for its regulation in both glucose and lipid metabolism. Mogrol was originally identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK and summarize the structure-activity relationships, a series of mogrol derivatives were designed, synthesized and evaluated in pharmacological AMPK activation assays. The results showed that the amine derivatives at the 24-position can improve the potency. Among them, compounds 3 and 4 exhibited the best potency (EC50 : 0.15 and 0.14 μM) which was 20 times more potent than mogrol (EC50 : 3.0 μM).