Abstract
Glaucumolides A (1) and B (2), novel biscembranes composed of an unprecedented α,β-unsaturated ε-lactone, along with the known metabolites ximaolide A (3) and isosarcophytonolide D (4), were isolated from the cultured soft coral Sarcophyton glaucum. The structures of the new metabolites were determined by extensive spectroscopic analyses. Compounds 1 and 2 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. In anti-inflammation assay, compounds 1 and 2 displayed strong inhibition of superoxide anion generation and elastase release in human neutrophils stimulated by fMLP/CB. Furthermore, both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and compounds 1-3 were found to effectively reduce the expression of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anthozoa / metabolism
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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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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cyclooxygenase 2 / biosynthesis
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Cyclooxygenase 2 / metabolism
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Cytochalasin B / adverse effects
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Diterpenes / chemistry
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Diterpenes / isolation & purification
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Diterpenes / pharmacology*
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Drug Screening Assays, Antitumor / methods*
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HL-60 Cells
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Humans
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Inflammation / drug therapy
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Lactones / chemistry
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Lactones / isolation & purification
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Leukemia, Promyelocytic, Acute / drug therapy*
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Lipopolysaccharides
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Macrophages / metabolism
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Mice
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Neutrophils / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Superoxides / chemistry
Substances
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Anti-Inflammatory Agents
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Antineoplastic Agents
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Diterpenes
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Lactones
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Lipopolysaccharides
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glaucumolide A
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glaucumolide B
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Superoxides
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Cytochalasin B
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Nitric Oxide Synthase Type II
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Ptgs2 protein, mouse
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Cyclooxygenase 2