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.
Copyright © 2017 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Survival / drug effects
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Cyclooxygenase 2 / metabolism
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Dose-Response Relationship, Drug
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Drug Design*
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Glycyrrhetinic Acid / chemical synthesis
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Glycyrrhetinic Acid / chemistry
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Glycyrrhetinic Acid / pharmacology*
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-6 / biosynthesis
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Mice
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Molecular Structure
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Nitric Oxide / antagonists & inhibitors*
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Nitric Oxide Synthase Type II / metabolism
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RAW 264.7 Cells
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-6
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Lipopolysaccharides
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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Glycyrrhetinic Acid