Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor.

Abstract

Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure-activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2'-fluoride group in ring B were essential for this class of compounds to be active against NMU2R.

• Authors: Ming-Liang Ma, Ming Li, Jiao-Jiao Gou, Tian-Yu Ruan, Hai-Shan Jin, Ling-Hong Zhang, Liang-Chun Wu, Xiao-Yan Li, Ying-He Hu, Ke Wen, Zheng Zhao
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 21 Pg. 6117-23 (Nov 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 25262941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Flavonoids
• Receptors, Neurotransmitter
• neuromedin U receptor

Topics

• Drug Design
• Flavonoids (chemical synthesis, chemistry, pharmacology)
• Humans
• Receptors, Neurotransmitter (agonists, metabolism)
• Structure-Activity Relationship