WS75624 A and B, New Endothelin Converting Enzyme Inhibitors Isolated from Saccharothrix sp. No. 75624 I. Taxonomy, Fermentation, Isolation, Physico-chemical Properties and Biological Activities

• Published in: Journal of antibiotics Vol. 48; no. 10; pp. 1066 - 1072
• Main Authors: TSURUMI, YASUHISA, UEDA, HIROTUGU, HAYASHI, KENICHI, TAKASE, SHIGEHIRO, NISHIKAWA, MOTOAKI, KIYOTO, SUMIO, OKUHARA, MASAKUNI
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1995; Japan Antibiotics Research Association
• Subjects: Animals; Antihypertensive agents; Aspartic Acid Endopeptidases - antagonists & inhibitors; Biological and medical sciences; Cardiovascular system; Cattle; Endothelin-Converting Enzymes; Fermentation; Male; Medical sciences; Metalloendopeptidases; Mice; Microbial Sensitivity Tests; Neprilysin - antagonists & inhibitors; Pharmacology. Drug treatments; Pyridines - chemistry; Pyridines - isolation & purification; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Saccharothrix; Swine; Thiazoles - chemistry; Thiazoles - isolation & purification; Thiazoles - pharmacology; Fungi; Antifungal agent; Microbial origin; Enzyme; Taxonomy; Enzyme inhibitor; Antihypertensive agent; Isolation; Fermentation; Biological activity; Physicochemical properties; Thallophyta
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.48.1066

Novel endothelin converting enzyme (ECE) inhibitors, WS75624 A and B, have been isolated from the fermentation broth of Saccharothrix sp. No. 75624. These inhibitors were purified from an acetone extract of whole culture broth followed by HP-20 column chromatography, silica gel column chromatography and HPLC. WS75624 A and B showed highly potent ECE inhibitory activity, and both had IC50 values of 0.03μg/ml. WS75624 A and B also showed other metalloprotease (collagenase and neutral endopeptidase) inhibitory activity with IC50 values of 1 μg/ml. Since large amount of WS75624 B was isolated, we tried in vivo evaluation using WS75624 B. WS75624 B inhibited big endothelin-induced pressor effect when administered to SD rat intravenously with big ET-1.