Abstract
Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)], and the third was a terphenyl compound, BTH-II0204-207:A (2). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound (3) was confirmed via single-crystal X-ray diffraction. Compounds 1-3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase (PDE4B2) inhibitory activities. The putative binding mode of 1-3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Ascomycota / chemistry*
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Ascomycota / classification
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Benzoquinones / chemistry
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Benzoquinones / isolation & purification*
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Benzoquinones / pharmacology*
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Candida albicans / drug effects
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Crystallography, X-Ray
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Cyclic Nucleotide Phosphodiesterases, Type 4 / drug effects*
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
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Drug Screening Assays, Antitumor
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Female
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Humans
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Microbial Sensitivity Tests
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Phosphodiesterase 4 Inhibitors / chemistry
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Phosphodiesterase 4 Inhibitors / isolation & purification*
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Phosphodiesterase 4 Inhibitors / pharmacology*
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Staphylococcus aureus / drug effects*
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Terphenyl Compounds / chemistry
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Terphenyl Compounds / isolation & purification*
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Terphenyl Compounds / pharmacology*
Substances
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Benzoquinones
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Phosphodiesterase 4 Inhibitors
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Terphenyl Compounds
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Cyclic Nucleotide Phosphodiesterases, Type 4