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

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. alpha,beta-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 mu M respectively). Furthermore, compound 6k could also significantly suppress LPS-induced iNOS and COX-2 expression and 1L-6 production through MAPKs and NF-kB signaling pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.