Abstract
Bioactivity-guided fractionation of an extract of Burkholderia thailandensis led to the isolation and identification of a new cytotoxic depsipeptide and its dimer. Both compounds potently inhibited the function of histone deacetylases 1 and 4. The monomer, spiruchostatin C (2), was tested side by side with the clinical depsipeptide FK228 (1, Istodax, romidepsin) in a murine hollow fiber assay consisting of 12 implanted tumor cell lines. Spiruchostatin C (2) showed good activity toward LOX IMVI melanoma cells and NCI-H522 non small cell lung cancer cells. Overall, however, FK228 (1) showed a superior in vivo antitumor profile in comparison to the new compound.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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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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Burkholderia / chemistry*
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Depsipeptides / chemistry
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Depsipeptides / isolation & purification*
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Depsipeptides / pharmacology*
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Drug Screening Assays, Antitumor
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Histone Deacetylase Inhibitors / chemistry
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Histone Deacetylase Inhibitors / isolation & purification*
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Histone Deacetylase Inhibitors / pharmacology*
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Humans
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Mice
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Molecular Structure
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National Cancer Institute (U.S.)
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United States
Substances
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Antineoplastic Agents
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Depsipeptides
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Histone Deacetylase Inhibitors
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spiruchostatin C
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romidepsin