Novel inhibitors of superoxide anion generation, OPC-15160 and OPC-15161. Taxonomy, fermentation, isolation, physico-chemical properties, biological characteristics and structure determination.
A new inhibitor of superoxide anion generation by guinea pig macrophages, OPC-15160, was isolated from the culture broth of fungus Thielavia minor OFR-1561, and a more potent inhibitor, OPC-15161, was obtained as a major degradation product of OPC-15160. OPC-15161 was five times more active than the natural inhibitor and its IC50 value was 2.8 x 10(-5) M. The structure of OPC-15161 was elucidated by X-ray analysis to be 6-(1H-indol-3-ylmethyl)-5-methoxy-3- (2-methylpropyl)-2-(1H)-pyrazinone, 4-oxide and had a novel and highly functionalized pyrazine skeleton.
Nakano
Y
Y
Third Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.
Kawaguchi
T
T
Sumitomo
J
J
Takizawa
T
T
Uetsuki
S
S
Sugawara
M
M
Kido
M
M
D000818:Animals; D001203:Ascomycota / Q000145:classification* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D006168:Guinea Pigs; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012995:Solubility; D013481:Superoxides / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
D011719:Pyrazines; D013481:Superoxides; C067708:OPC 15161; C067707:OPC 15160