BW A4C AND OTHER HYDROXAMIC ACIDS ARE POTENT INHIBITORS OF LINOLEIC-ACID 8R-DIOXYGENASE OF THE FUNGUS GAEUMANNOMYCES-GRAMINIS

Linoleic acid is converted to 8R-hydroperoxylinoleic acid by the solub le 8R-dioxygenase of the fungus Gaeumannomyces graminis. Effects of di fferent lipoxygenase inhibitors on the 8R-dioxygenase were evaluated. Three hydroxamic acid derivatives were investigated. BW A4C (N-(3-phen oxycinnamyl)acetohydroxamic acid) was the most potent with an IC50 of 0.2 mu M, followed by zileuton (3-10 mu M) and linoleate-hydroxamic ac id (0.02 mM). Two other lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, were less potent (IC50 0.09 and 0.15 m M, respectively). The 8R-dioxygenase was also strongly inhibited by co mmonly used buffer additives, dithiothreitol, beta-mercaptoethanol and phenylmethylsulfonyl fluoride. G. graminis also contains a hydroperox ide isomerase, which converts 8R-hydroperoxylinoleic acid to 7S,8S-dih ydroxylinoleic acid. Ammonium sulphate precipitation and gel filtratio n indicated that the dioxygenase and the hydroperoxide isomerase activ ities could be separated.