WS79089A, B and C, new endothelin converting enzyme inhibitors isolated from Streptosporangium roseum. No. 79089. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.
WS79089A, B and C, which are novel endothelin converting enzyme (ECE) inhibitors have been isolated from the fermentation broth of Streptosporangium roseum No. 79089. These inhibitors were purified from an acetone extract of whole culture broth followed by Silicar CC-4 column chromatography and HPLC. WS79089A, B and C showed highly selective ECE inhibition activity with IC50 values of 0.73 microM 0.14 microM and 3.42 microM, respectively. On the basis of spectroscopic and chemical evidence, the tentative structures of WS79089A, B and C have been proposed, they have benzo[a]naphtacen chromophores.
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Y
Y
Tsurumi
N
N
Ohhata
T
T
Iwamoto
N
N
Shigematsu
K
K
Sakamoto
M
M
Nishikawa
S
S
Kiyoto
M
M
Okuhara
D000192:Actinomycetales / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001419:Bacteria / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002417:Cattle; D002478:Cells, Cultured; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005285:Fermentation; D005658:Fungi / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008666:Metalloendopeptidases; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D051381:Rats; D012988:Soil Microbiology; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013754:Tetracyclines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D013754:Tetracyclines; C088493:WS 79089A; C088494:WS 79089B; C088495:WS 79089C; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon