Abstract
We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 μM. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-κB and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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 / pharmacology
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Cell Line
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Curcumin / analogs & derivatives*
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Curcumin / chemical synthesis
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Curcumin / pharmacology
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Dose-Response Relationship, Drug
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Drug Discovery
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression
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Inflammation
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Lipopolysaccharides / pharmacology
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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NF-kappa B / agonists
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Piperidones / chemical synthesis*
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Piperidones / pharmacology
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Sepsis / chemically induced
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Sepsis / metabolism
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Sepsis / mortality
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Sepsis / prevention & control*
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Signal Transduction
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Structure-Activity Relationship
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Survival Analysis
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Lipopolysaccharides
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NF-kappa B
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Piperidones
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Extracellular Signal-Regulated MAP Kinases
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Curcumin