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

被引：9

作者：

BRODOWSKY, ID ^{[1
]}

HAMBERG, M ^{[1
]}

OLIW, EH ^{[1
]}

机构：

[1] KAROLINSKA INST, DEPT PHYSIOL CHEM, SOLNA, SWEDEN

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1994年 / 254卷 / 1-2期

关键词：

DIOXYGENASE; HYDROPEROXIDE ISOMERASE; LIPOXYGENASE INHIBITOR; HYDROXAMIC ACID;

D O I：

10.1016/0014-2999(94)90368-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 mu M, followed by zileuton (3-10 mu M) 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 phenylmethylsulfonyl 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.

引用

页码：43 / 47

页数：5

共 23 条

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