Abstract
In our ongoing search for new bioactive metabolites from microbial resources, Aspergillus terreus (HKI0499) was examined by chemical metabolite profiling. Together with the known butyrolactone I ( 3), the unusual sulfate derivatives butyrolactone I 3-sulfate ( 1) and butyrolactone I 4''-sulfate ( 2) were discovered. The chemical structures were determined by NMR and MS data analyses. All compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3alpha/beta kinases; compounds 2 and 3 were also evaluated for their cytotoxic and antiproliferative activities. Butyrolactone I 3-sulfate ( 1) exhibited specific inhibitory activity against CDK1/cyclin B and CDK5/p25, yet 15-30-fold less than butyrolactone I ( 3). Likewise, butyrolactone I 3-sulfate ( 1) exhibited moderate cytotoxicity solely against HeLa cells (CC 50 = 80.7 microM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives*
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4-Butyrolactone / chemistry
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4-Butyrolactone / isolation & purification
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4-Butyrolactone / pharmacology
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Animals
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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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Aspergillus / chemistry*
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Brain / enzymology
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CDC2 Protein Kinase / antagonists & inhibitors
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Cyclin-Dependent Kinase 5 / antagonists & inhibitors
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Drug Screening Assays, Antitumor
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Dyrk Kinases
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Humans
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Oocytes / enzymology
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Starfish / enzymology
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Sulfates / chemistry*
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Swine
Substances
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Antineoplastic Agents
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Sulfates
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butyrolactone I
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Protein-Tyrosine Kinases
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Cyclin-Dependent Kinase 5
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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Glycogen Synthase Kinase 3
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4-Butyrolactone