Trypanosomatid iron-superoxide dismutase inhibitors. Selectivity and mechanism of N1,N6-bis(2,3-dihydroxybenzoyl)-1,6-diaminohexane.
Crithidia, like trypanosomes and leishmania, has an iron-containing superoxide dismutase. The iron chelator N1,N6-bis (dihydroxybenzoyl)-1,6-diaminohexane proved to be a potent inhibitor of this enzyme. Inhibition of the crithidial superoxide dismutase by this compound was dependent on the presence of oxygen and associated with the formation of a complex which could not be dissociated by gel-filtration chromatography. We propose that this biscatecholic inhibitor is first oxidized to a quinone which then covalently modifies a nucleophilic residue on the enzyme. This compound was less effective as an inhibitor of a mammalian copper- and zinc-containing superoxide dismutase. Thus, this inhibitor could serve as a prototype for the design of antiparasitic agents.
D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology*; D002850:Chromatography, Gel; D003300:Copper; D003421:Crithidia / Q000201:enzymology*; D003959:Diamines / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007501:Iron; D010084:Oxidation-Reduction; D010100:Oxygen; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*; D015032:Zinc
D002614:Chelating Agents; D003959:Diamines; D062385:Hydroxybenzoates; C046415:N(1),N(6)-bis(2,3-dihydroxybenzoyl)-1,6-diaminohexane; D003300:Copper; D007501:Iron; D013482:Superoxide Dismutase; D015032:Zinc; D010100:Oxygen