1-thiocarbamoyl-2-imidazolidinone, a metabolite of niridazole in Schistosoma mansoni

Abstract

Niridazole, a nitro heterocyclic antischistosomal drug, is extensively metabolized to unknown metabolites by Schistosoma mansoni. We report that 1-thiocarbamoyl-2-imidazolidinone was isolated by high pressure liquid chromatography and identified by high resolution electron impact mass spectroscopy as a niridazole metabolite in schistosomes. After a 20-h in vitro incubation in 30 ml of medium containing 10 micrograms ml-1 [14C]niridazole (5.2 Ci mol-1), 100 S. mansoni worm pairs contained approximately 275 ng of 1-thiocarbamoyl-2-imidazolidinone. This amount represented 4% of the total metabolized fraction of niridazole in the parasite. Incubation of schistosomes with 1-thiocarbamoyl-2-[2 14C]imidazolidinone (2.7 Ci mol-1) indicated that this metabolite was not taken up. However, schistosomes released an average of 44 ng ml-1 or 1% of the total 1-thiocarbamoyl-2-imidazolidinone found in the worm back into 1 ml of medium during incubation. No host oxidative metabolites of niridazole were found in the parasites.