Tsurumi Y, Ueda H, Hayashi K, Takase S, Nishikawa M, Kiyoto S, Okuhara M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
J Antibiot (Tokyo). 1995 Oct;48(10):1066-72. 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 0.03 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.
新型内皮素转化酶（ECE）抑制剂WS75624 A和B，是从糖丝菌属75624号菌株的发酵液中分离得到的。这些抑制剂是从全培养液的丙酮提取物中纯化出来的，随后经过HP - 20柱色谱、硅胶柱色谱和高效液相色谱法。WS75624 A和B表现出高效的ECE抑制活性，两者的半数抑制浓度（IC50）值均为0.03微克/毫升。WS75624 A和B还表现出对其他金属蛋白酶（胶原酶和中性内肽酶）的抑制活性，IC50值为1微克/毫升。由于分离得到了大量的WS75624 B，我们尝试使用WS75624 B进行体内评估。当将WS75624 B与大内皮素-1一起静脉注射给SD大鼠时，它能抑制大内皮素诱导的升压作用。
