Abstract
Inflammatory cytokines, such as interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α), induce the intracellular signaling pathway leading to the activation of nuclear factor κB (NF-κB). A series of eudesmane-type sesquiterpene lactones possessing an α-methylene γ-lactone group and/or an α-bromo ketone group were synthesized and evaluated for their inhibitory effects on the NF-κB-dependent gene expression and signaling pathway. Our present study reveals that eudesmane-type α-methylene γ-lactones and α-bromo ketones inhibit multiple steps in the NF-κB signaling pathway induced by IL-1α and TNF-α.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Algorithms
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods
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Cytokines / metabolism*
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Dimerization
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Drug Design
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Humans
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Inflammation / drug therapy
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Inhibitory Concentration 50
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Intercellular Adhesion Molecule-1 / biosynthesis
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Interleukin-1alpha / metabolism
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Ketones / chemistry
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Lactones / chemistry*
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Models, Chemical
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NF-kappa B / metabolism*
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Sesquiterpenes / chemistry*
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Sesquiterpenes, Eudesmane / pharmacology*
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Signal Transduction
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Cytokines
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Interleukin-1alpha
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Ketones
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Lactones
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NF-kappa B
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Sesquiterpenes
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Sesquiterpenes, Eudesmane
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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eudesmane