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.