WS75624-A AND WS75624-B, NEW ENDOTHELIN-CONVERTING ENZYME-INHIBITORS ISOLATED FROM SACCHAROTHRIX SP NO-75624 .1. TAXONOMY, FERMENTATION, ISOLATION, PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL-ACTIVITIES

Novel endothelin converting enzyme (ECE) inhibitors, WS75624 A and Bt, have been isolated from the fermentation broth of Saccharothrix sp. N o. 75624. These inhibitors were purified from an acetone extract of wh ole culture broth followed by HP-20 column chromatography, silica gel column chromatography and HPLC. WS75624 A and B showed highly potent E CE inhibitory activity, and both had IC50 values of 0.03 mu g/ml. WS75 624 A and B also showed other metalloprotease (collagenase and neutral endopeptidase) inhibitory activity with IC50 values of 1 mu g/ml. Sin ce large amount of WS75624 B was isolated, we tried in vivo evaluation using WS75624 B. WS75624 B inhibited big endothelin-induced presser e ffect when administered to SD rat intravenously with big ET-1.