title: Nitrofuran inhibition of yeast and rat tissue glutathione reductases. Structure-activity relationships.
abstract: Nitrofuran derivatives bearing unsaturated five- or six-membered nitrogen heterocycles or related substituents were more effective inhibitors of yeast and rat tissue glutathione reductases than those bearing other groups, such as nifurtimox, nitrofurazone and 5-nitro-2-furoic acid. The inhibitory action proved independent of electron withdrawal from the reduced enzyme, as a consequence of redoxcycling of the nitro group. Uncompetitive kinetics was obtained with nitrofurantoin and nifurtimox. Most of the assayed nitrofurans inhibited the yeast enzyme Coenzyme A glutathione disulfide reductase activity, though less than oxidized glutathione reduction. The transhydrogenase activity was not inhibited to a significant degree. Benznidazole (a 2-nitroimidazole derivative), 2-nitroimidazole, 5-nitroindole and chloramphenicol did not inhibit glutathione reductase. Under the same experimental conditions, liver glutathione peroxidase was not affected by the nitro compounds.
authors.affiliation: Centro de Investigaciones Bioenergéticas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Grinblat
authors.forename: C M
authors.initials: CM
authors.lastname: Sreider
authors.forename: A O
authors.initials: AO
authors.lastname: Stoppani
mesh_terms: D000818:Animals; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009581:Nitrofurans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D009581:Nitrofurans; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase