B-90063, a Novel Endothelin Converting Enzyme Inhibitor Isolated from a New Marine Bacterium, Blastobacter sp. SANK 71894
| Autor: | Yoichi Matsushita, Aiya Sato, Tohru Watanabe, Takeshi Kinoshita, Yasuyuki Takamatsu, Momoyo Tanaka, Sachiko Takaishi, Kentaro Kodama, Hideyuki Haruyama, Yasuteru Iijima, Teruaki Negishi, Naoko Tuchiya |
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| Rok vydání: | 1998 |
| Předmět: |
medicine.hormone
Magnetic Resonance Spectroscopy food.ingredient Pyridones Endothelin converting enzyme 1 Endothelin-Converting Enzymes Matrix Metalloproteinase Inhibitors Sulfides Biology Endothelins Structure-Activity Relationship food Gram-Negative Bacteria Drug Discovery medicine Animals Aspartic Acid Endopeptidases Humans Protease Inhibitors education Receptor Pharmacology chemistry.chemical_classification education.field_of_study Endothelin-1 Molecular Structure Receptors Endothelin Metalloendopeptidases Biological activity Receptor Endothelin A Receptor Endothelin B Rats Enzyme Mechanism of action Biochemistry chemistry Enzyme inhibitor Fermentation biology.protein Cattle Neprilysin Blastobacter medicine.symptom Water Microbiology |
| Zdroj: | The Journal of Antibiotics. 51:805-815 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.51.805 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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