Histone deacetylase inhibitors from Burkholderia thailandensis.

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.

[1]  M. Hällbrink,et al.  Metallic Zinc Reduction of Disulfide Bonds between Cysteine Residues in Peptides and Proteins , 2005, International Journal of Peptide Research and Therapeutics.

[2]  Minoru Yoshida,et al.  FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. , 2002, Cancer research.

[3]  G. Szókán,et al.  Configuration and racemization determination of cysteine residues in peptides by chiral derivatization and HPLC: application to oxytocin peptides , 2001, Journal of peptide science : an official publication of the European Peptide Society.

[4]  H. Tanaka,et al.  FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination. , 1994, The Journal of antibiotics.

[5]  M R Grever,et al.  In vivo cultivation of tumor cells in hollow fibers. , 1995, Life sciences.

[6]  D. Scudiero,et al.  Separation and SAR study of HIF-1alpha inhibitory tubulosines from Alangium cf. longiflorum. , 2008, Planta medica.

[7]  R. Shoemaker.  The NCI60 human tumour cell line anticancer drug screen , 2006, Nature Reviews Cancer.

[8]  D. Scudiero,et al.  Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. , 1988, Cancer research.

[9]  Minoru Yoshida,et al.  Total synthesis of the bicyclic depsipeptide HDAC inhibitors spiruchostatins A and B, 5''-epi-spiruchostatin B, FK228 (FR901228) and preliminary evaluation of their biological activity. , 2009, Chemistry.

[10]  Franz-Josef Meyer-Almes,et al.  Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-spectrum Antiproliferative Activities , 2022 .

[11]  John H Cardellina,et al.  Identification of a new natural camptothecin analogue in targeted screening for HIF-1alpha inhibitors. , 2006, Planta medica.

[12]  M. Nishiyama,et al.  Histone deacetylase as a new target for cancer chemotherapy , 2001, Cancer Chemotherapy and Pharmacology.

[13]  S. Minucci,et al.  Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer , 2006, Nature Reviews Cancer.

[14]  M. K. Pflum,et al.  Isoform-selective histone deacetylase inhibitors. , 2008, Chemical Society reviews.

[15]  S. Moon,et al.  Plant growth promoting and fungicidal 4-quinolinones from Pseudomonas cepacia , 1996 .

[16]  K. Shin‐ya,et al.  Spiruchostatins A and B, novel gene expression-enhancing substances produced by Pseudomonas sp. , 2001 .

[17]  M. Shibazaki,et al.  YM-30059, a novel quinolone antibiotic produced by Arthrobacter sp. , 1996, The Journal of antibiotics.

[18]  Nicholas H Oberlies,et al.  Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma , 2011, The Journal of Antibiotics.