title: Histone deacetylase inhibitors from Burkholderia thailandensis.
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.
authors.affiliation: Natural Products Support Group, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, United States. klausmeyerp@mail.nih.gov
authors.forename: Paul
authors.initials: P
authors.lastname: Klausmeyer
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Shipley
authors.forename: Karina M
authors.initials: KM
authors.lastname: Zuck
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McCloud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019117:Burkholderia / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D054547:National Cancer Institute (U.S.); D014481:United States
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; C568645:spiruchostatin C; C087123:romidepsin