1998 Volume 51 Issue 9 Pages 805-815
A novel endothelin-converting enzyme (ECE) inhibitor, B-90063, was isolated from the culture supernatant of the newly discovered marine bacterium Blastobacter sp. SANK 71894. Based on spectral analyses and chemical reactions, the structure of B-90063 was determined to be bis[6-formyl-4-hydroxy-2-(2′-n-pentyloxazol-4′-yl)-4-pyridon-3-yl]-disulfide (1a). Human and rat ECEs were inhibited more potently by B-90063, with respective IC50 values of 1.0 and 3.2 μM, than were other neutral endopeptidases such as NEP and type-I and -IV collagenases. B-90063 also inhibited the binding of ET-1 to rat ETA and bovine ETB receptors, though its antagonistic activities were weak. B-90063, thus, may abolish the physiological actions of endothelins through the ECE inhibitory and receptor antagonistic mechanisms.