Takaishi S, Tuchiya N, Sato A, Negishi T, Takamatsu Y, Matsushita Y, Watanabe T, Iijima Y, Haruyama H, Kinoshita T, Tanaka M, Kodama K
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
J Antibiot (Tokyo). 1998 Sep;51(9):805-15. doi: 10.7164/antibiotics.51.805.
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 microM, 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 ET(A) and bovine ET(B) 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.
一种新型内皮素转化酶（ECE）抑制剂B-90063，是从新发现的海洋细菌Blastobacter sp. SANK 71894的培养上清液中分离得到的。基于光谱分析和化学反应，确定B-90063的结构为双[6-甲酰基-4-羟基-2-(2'-正戊基恶唑-4'-基)-4-吡啶酮-3-基]-二硫化物（1a）。与其他中性内肽酶如中性肽链内切酶（NEP）以及I型和IV型胶原酶相比，B-90063对人和大鼠ECE的抑制作用更强，其IC50值分别为1.0和3.2微摩尔。B-90063还抑制ET-1与大鼠ET(A)和牛ET(B)受体的结合，不过其拮抗活性较弱。因此，B-90063可能通过ECE抑制和受体拮抗机制消除内皮素的生理作用。
