The metabolism of nitrophenolic and 5-arylazorhodanine anthelmintics by Ascaris suum, Moniezia expansa and by mouse- and sheep-liver enzymes.
1. The anthelmintics disophenol (2,6-diiodo-4-nitrophenol), nitroxynil (3-iodo-4-hydroxy-5-nitrobenzonitrile) and nitrodan (3-methyl-5-(4-nitrophenylazo)rhodanine) were reduced in vitro to the corresponding amines by intact Ascaris suum, Moniezia expansa, by enzymes prepared from these helminths, and by mouse- and sheep-liver homogenates. Helminth reductases required NADH2 and glutathione as cofactors and were inhibited about 50% by 2.0 x 10(-7) M allopurinol. Azo bonds of nitrodan and its analogues were not reduced by the helminths but were reduced by mouse- and sheep-liver enzymes. 2. Mouse- and sheep-liver enzymes, in addition to effecting nitro reduction, metabolized nitroxynil by hydrolysis to 3-iodo-4-hydroxy-5-nitrobenzamide and 3-iodo-4-hydroxy-5-nitrobenzoic acid. No hydroxylation products were found. Nitrodan was oxidized by the mammalian microsomal oxidation enzyme system to the thiazolidinedione derivative, but not by helminth enzymes.
D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D001200:Ascaris / Q000378:metabolism*; D002589:Cestoda / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008989:Monieziasis / Q000469:parasitology; D009596:Nitrophenols / Q000378:metabolism*; D009611:Nitroxinil / Q000378:metabolism; D012236:Rhodanine / Q000031:analogs & derivatives / Q000378:metabolism*; D012756:Sheep; D013045:Species Specificity; D013844:Thiazoles / Q000378:metabolism*
D000871:Anthelmintics; D009596:Nitrophenols; D013844:Thiazoles; D012236:Rhodanine; D009611:Nitroxinil