Abstract
CXCL10 (IP-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells such as macrophages and T-lymphocytes and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 (MM6) cells, the new diaryl ether 3'-demethyldihydromaldoxin (1) along with the known compound dihydromaldoxin (2), were isolated from fermentations of a Steganospora species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds (1) and (2) inhibited lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced CXCL10 promoter activity in transiently transfected MM6 cells in a dose-dependent manner with IC(50) values of 39-41 μM and also reduced LPS/IFN-γ-induced CXCL10 protein synthesis and excretion.
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 / chemistry
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Anti-Inflammatory Agents / isolation & purification*
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Anti-Inflammatory Agents / pharmacology
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Cell Line
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Cell Survival / drug effects
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Chemokine CXCL10 / antagonists & inhibitors
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Chemokine CXCL10 / metabolism*
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Dose-Response Relationship, Drug
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Fungi / chemistry*
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Humans
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Inhibitory Concentration 50
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Lactones / chemistry
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Lactones / isolation & purification*
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Lactones / pharmacology
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Phenyl Ethers / chemistry
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Phenyl Ethers / isolation & purification*
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Phenyl Ethers / pharmacology
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Spectrometry, Mass, Electrospray Ionization
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Spiro Compounds / chemistry
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Spiro Compounds / isolation & purification*
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Spiro Compounds / pharmacology
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Transfection
Substances
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Anti-Inflammatory Agents
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Chemokine CXCL10
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Lactones
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Phenyl Ethers
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Spiro Compounds
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maldoxin