2. Academic Validation
  3. Design, synthesis and biological evaluation of mogrol derivatives as a novel class of AMPKα2β1γ1 activators

Design, synthesis and biological evaluation of mogrol derivatives as a novel class of AMPKα2β1γ1 activators

  • Bioorg Med Chem Lett. 2020 Jan 15;30(2):126790. doi: 10.1016/j.bmcl.2019.126790.
Junwei Wang 1,  Junhua Liu 1,  Zhifu Xie 2,  Jia Li 2,  Jingya Li 3,  Lihong Hu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
  • 2 Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jyli@mail.shcnc.ac.cn.
  • 4 Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: lhhu@njucm.edu.cn.
PMID: 31744674 DOI: 10.1016/j.bmcl.2019.126790
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).

Keywords

AMPK; AMPKα2β1γ1 activators; Mogrol derivatives; Structure-activity relationships.

Figures