Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay

We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell l...

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Veröffentlicht in:	Journal of antibiotics 2000/07/25, Vol.53(7), pp.657-663
Hauptverfasser:	STEAD, PAUL, LATIF, SHAZIA, BLACKABY, ANDREW P., SIDEBOTTOM, PHILIP J., DEAKIN, ANGELA, TAYLOR, NICHOLAS L., LIFE, PAUL, SPAULL, JOHN, BURRELL, FIONA, JONES, ROSIE, LEWIS, JANE, DAVIDSON, IAN, MANDER, THOMAS
Format:	Artikel
Sprache:	eng
Schlagworte:	Alkaline phosphatase Alkaline Phosphatase - drug effects Alkaline Phosphatase - genetics Alkaline Phosphatase - metabolism ansamycin Ansamycins Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology Antibiotics (antibacterial agents, antifungal agents) Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents Applied microbiology Benzoquinones Biological and medical sciences Cell Line Cell Survival - drug effects Drug Evaluation, Preclinical - methods Fundamental and applied biological sciences. Psychology Humans Inhibitory Concentration 50 Interleukin-6 - metabolism Interleukin-6 - pharmacology Lactams, Macrocyclic Lung - cytology Lung - drug effects Microbiology Oncostatin M Peptides - metabolism Protein Biosynthesis Proteins - drug effects Quinones - chemistry Quinones - metabolism Quinones - pharmacology Recombinant Proteins - drug effects Recombinant Proteins - genetics Recombinant Proteins - metabolism Rifabutin - chemistry Rifabutin - pharmacology Signal Transduction Streptomyces Streptomyces - metabolism
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Zusammenfassung:	We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties.
ISSN:	0021-8820 1881-1469
DOI:	10.7164/antibiotics.53.657