Abstract
Four new alkaloids, including two new meleagrin analogs, meleagrin D (1) and E (2), and two new diketopiperazines, roquefortine H (3) and I (4), were isolated from a deep ocean sediment-derived fungus Penicillium sp. Meleagrin D (1) and E (2) possess unprecedented acetate-mevalonate-derived side chains on the imidazole moiety. These new meleagrins showed weak cytotoxicity against the A-549 cell line, whereas meleagrin B (5) and meleagrin (6), which were isolated previously from the same strain, induced HL-60 cell apoptosis or arrested the cell cycle through G(2)/M phase, respectively. The results indicate that the distinct substitutions on the imidazole ring significantly influence the cytotoxicity of the meleagrin alkaloids.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry
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Alkaloids / isolation & purification*
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Alkaloids / 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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Apoptosis / drug effects
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Cell Cycle / drug effects
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Cell Survival / drug 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
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Flow Cytometry
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Geologic Sediments
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HL-60 Cells
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Humans
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Imidazoles / chemistry
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Imidazoles / isolation & purification
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Imidazoles / pharmacology
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Nuclear Magnetic Resonance, Biomolecular
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Penicillium / chemistry*
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Soil Microbiology*
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Spectrometry, Mass, Electrospray Ionization
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Spectrophotometry, Infrared
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Spectrophotometry, Ultraviolet
Substances
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Alkaloids
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Antineoplastic Agents
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Diterpenes
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Imidazoles