title: BW A4C and other hydroxamic acids are potent inhibitors of linoleic acid 8R-dioxygenase of the fungus Gaeumannomyces graminis.
abstract: Linoleic acid is converted to 8R-hydroperoxylinoleic acid by the soluble 8R-dioxygenase of the fungus Gaeumannomyces graminis. Effects of different lipoxygenase inhibitors on the 8R-dioxygenase were evaluated. Three hydroxamic acid derivatives were investigated. BW A4C (N-(3-phenoxycinnamyl)acetohydroxamic acid) was the most potent with an IC50 of 0.2 microM, followed by zileuton (3-10 microM) and linoleate-hydroxamic acid (0.02 mM). Two other lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, were less potent (IC50 0.09 and 0.15 mM, respectively). The 8R-dioxygenase was also strongly inhibited by commonly used buffer additives, dithiothreitol, beta-mercaptoethanol and phenylmethanesulfonyl fluoride. G. graminis also contains a hydroperoxide isomerase, which converts 8R-hydroperoxylinoleic acid to 7S,8S-dihydroxylinoleic acid. Ammonium sulphate precipitation and gel filtration indicated that the dioxygenase and the hydroperoxide isomerase activities could be separated.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University Biomedical Center, Sweden.
authors.forename: I D
authors.initials: ID
authors.lastname: Brodowsky
authors.forename: M
authors.initials: M
authors.lastname: Hamberg
authors.forename: E H
authors.initials: EH
authors.lastname: Oliw
mesh_terms: D044482:Benzeneacetamides; D002021:Buffers; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D013098:Xylariales / Q000201:enzymology*
chemical_list: D044482:Benzeneacetamides; D002021:Buffers; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D005979:Glutathione Peroxidase; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C021377:hydroperoxide isomerase; D005978:Glutathione