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.