Abstract
Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were mainly determined by analysis of NMR and MS data, along with chemical methods. Preliminary screening for anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells showed that compounds 1, 2, and 5 inhibited the production of nitric oxide (NO) with IC50 values of 37.8, 7.1, and 42.5 μM, respectively. Compound 2 also inhibited NO production in LPS-stimulated RAW264.7 murine macrophages with an IC50 value of 27.0 μM. Moreover, these inhibitory effects correlated with the suppressive effect of compound 2 on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 and BV2 cells. In addition, compounds 2 and 5 significantly inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with the same IC50 value (8.2 μM).
Keywords:
Anti-inflammatory; Marine-derived fungus; PTP1B; Penicillium.
Copyright © 2014 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 / 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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Cyclooxygenase 2 / metabolism
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology
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Fatty Acids, Unsaturated / chemistry*
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Fatty Acids, Unsaturated / isolation & purification
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Fatty Acids, Unsaturated / pharmacology
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Lipopolysaccharides / toxicity
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism
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Magnetic Resonance Spectroscopy
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Mice
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Molecular Conformation
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Penicillium / chemistry
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Penicillium / metabolism*
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Tetrahydronaphthalenes / chemistry*
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Tetrahydronaphthalenes / isolation & purification
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Tetrahydronaphthalenes / pharmacology
Substances
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Anti-Inflammatory Agents
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Enzyme Inhibitors
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Fatty Acids, Unsaturated
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Lipopolysaccharides
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Tetrahydronaphthalenes
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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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Protein Tyrosine Phosphatase, Non-Receptor Type 1