NOVEL INHIBITORS OF SUPEROXIDE ANION GENERATION, OPC-15160 AND OPC-15161

TAXONOMY, FERMENTATION, ISOLATION, PHYSICO-CHEMICAL PROPERTIES, BIOLOGICAL CHARACTERISTICS AND STRUCTURE DETERMINATION

Abstract

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 × 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.