C. Y. Wang, C. Chiu, G. Bryan
Sep 1, 1975
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0
Influential Citations
25
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract Nitroreduction of anthelmintic and carcinogenic 5-nitrothiophenes, 4-(2,3-dihydroxypropyl-amino)-2-(5-nitro-2-thienyl) quinazoline and 4-(2-hydroxyethylamino)-2-(5-nitro-2-thienyl)quinazoline, by rat tissues was studied. A procedure for photometric determination of 5-nitro- and 5-aminothiophenes was described. Nitroreduction of 5-nitrothiophenes was catalyzed by rat liver cytosol and microsomes. Cytosol enzyme activity was hypoxanthine-dependent and inhibited by air and allopurinol. Microsomal enzyme activity was NADPH-dependent and inhibited by air. The reaction was also catalyzed by a purified milk xanthine oxidase. Since 5-nitrofurans and 5-nitrothiophenes have great similarity in structure and chemical properties, their nitroreduction may be catalyzed by the same enzymes, namely xanthine oxidase and NADPH-cytochrome c reductase. Nitroreductase activities of rat small intestine and liver were higher than those of kidney and stomach, suggesting that the small intestine and liver were the main organs for metabolism of 5-nitrothiophenes. Depending upon the source of enzyme, only 25–50 per cent of the reduced 5-nitrothiophene was converted to the corresponding amine. The rest of the reduced product may exist as reduced intermediates or bind to protein. Nitroreduction of several 5-nitrofurans was also measured.