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.
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 0.03 microgram/ml. WS75624 A and B also showed other metalloprotease (collagenase and neutral endopeptidase) inhibitory activity with IC50 values of 1 microgram/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.
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002417:Cattle; D000072396:Endothelin-Converting Enzymes; D005285:Fermentation; D008297:Male; D008666:Metalloendopeptidases; D051379:Mice; D008826:Microbial Sensitivity Tests; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013844:Thiazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D011725:Pyridines; D013844:Thiazoles; C096926:WS 75624 A; C096927:WS 75624 B; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D000072396:Endothelin-Converting Enzymes