The metabolism of nitrophenolic and 5-arylazorhodanine anthelmintics by Ascaris suum, Moniezia expansa and by mouse- and sheep-liver enzymes

Abstract

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 × 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.