Novel unsaturated glycyrrhetic acids derivatives: Design, synthesis and anti-inflammatory activity

  • Eur J Med Chem. 2017 Oct 20;139:337-348. doi: 10.1016/j.ejmech.2017.08.002.
Bo Li  1 ,  Shi Cai  1 ,  Yong-An Yang  2 ,  Shi-Chao Chen  1 ,  Rui Chen  1 ,  Jing-Bo Shi  1 ,  Xin-Hua Liu  3 ,  Wen-Jian Tang  4
Affiliations
  • 1. School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China.
  • 2. Elion Nature Biological Technology Co., Ltd, Nanjing 210038, China.
  • 3. School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
  • 4. School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
PMID: 28803048 DOI: 10.1016/j.ejmech.2017.08.002
Abstract

To develop novel anti-inflammatory agents, a series of unsaturated glycyrrhetic acids were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. The structure-activity relationship (SAR) of NO inhibitory activity was analyzed. α,β-Unsaturated glycyrrhetic acids showed better activity, among them, compounds 6k and 6l with piperazine unit exhibited the most potent nitric oxide (NO) and interleukin-6 (IL-6) inhibitory activity (IC50 = 13.3 and 15.5 μM respectively). Furthermore, compound 6k could also significantly suppress LPS-induced iNOS and COX-2 expression and IL-6 production through MAPKs and NF-kB signaling pathway.

Keywords
Anti-inflammatory activity; Glycyrrhetic acid; Structure-activity relationship; Unsaturated carbonyl.
Products