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Novel unsaturated glycyrrhetic acids derivatives: Design, synthesis and anti-inflammatory activity
Bo Li1, Shi Cai1, Yong-An Yang2
1School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China.
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.
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