Nitrofuran inhibition of yeast and rat tissue glutathione reductases. Structure-activity relationships.
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.
Grinblat
L
L
Centro de Investigaciones Bioenergéticas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Sreider
C M
CM
Stoppani
A O
AO
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
D009581:Nitrofurans; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase