title: NO scavenging by 3-hydroxyanthranilic acid and 3-hydroxykynurenine: N-nitrosation leads via oxadiazoles to o-quinone diazides.
abstract: The tryptophan metabolites kynurenine, 3-hydroxykynurenine, anthranilic, 3-hydroxyanthranilic and 3-methoxyanthranilic acids were compared with regard to diazotation by .NO or NO+, using three different donors, nitrite at pH 5, PAPA-NONOate at pH 7.4 and NO+SbF(6)- at pH 2.0. With all three sources of NO species, 3-hydroxykynurenine and 3-hydroxyanthranilic acid were readily nitrosated, thereby forming an intensely yellow compound. Nitrosation of the non-hydroxylated analogs did not lead to colored products within the period of observation. Competition experiments, using PAPA-NONOate as NO donor, showed that 3-hydroxyanthranilic acid is a more potent NO scavenger than N-acetylcysteine. Nitrosation of 3-hydroxykynurenine and 3-hydroxyanthranilic acid leads, presumably via a nitrosamine intermediate, to a diazonium ion, which forms an oxadiazole tautomerizing to a yellow o-quinone diazide. While the diazonium-derived quinone diazide is apparently the sole product detected directly after incubation of 3-hydroxyanthranilic acid, additional substances are formed from 3-hydroxykynurenine. Contrary to rapid carbenium ion formation from diazonium ions of non-hydroxylated anilines, nitrogen is practically not released from oxadiazoles/quinone diazides at moderate temperatures. Since carbenium ions are known to cause adduct formation with other biomolecules, and since non-hydroxylated anilines and their aminophenol analogs differ in their reactions following diazotation, these findings should be of relevance for the relative toxicity of anilines.
authors.affiliation: Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Berliner Strasse 28, D-37073 Goettingen, Lower Saxony, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Backhaus
authors.forename: Hafizur
authors.initials: H
authors.lastname: Rahman
authors.forename: Sebastian
authors.initials: S
authors.lastname: Scheffler
authors.forename: Hartmut
authors.initials: H
authors.lastname: Laatsch
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hardeland
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology; D000627:Aminophenols; D002855:Chromatography, Thin Layer; D003979:Diazonium Compounds / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006834:Hydrazines; D007249:Inflammation; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D009569:Nitric Oxide; D009573:Nitrites; D015538:Nitrosation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010069:Oxadiazoles / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: D000627:Aminophenols; D003979:Diazonium Compounds; D016166:Free Radical Scavengers; D006834:Hydrazines; D009573:Nitrites; D010069:Oxadiazoles; C112653:PAPA NONOate; D011809:Quinones; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D009569:Nitric Oxide; D007737:Kynurenine; D014364:Tryptophan; D000111:Acetylcysteine