The antischistosomal activity of oltipraz

Abstract

Administration of a single oral dose of oltipraz (5-(2-pyrazinyl)-4 methyl-1,2 dithiol-3-thione) to mice infected with Schistosoma mansoni resulted in the elimination of the parasites. Oltipraz is a slow-acting drug and approximately 2 months are required until its full schistosomicidal effect becomes evident. One of the earliest effects of the drug is a reduction of the glutathione stores of the worms. The antischistosomal activity of oltipraz is lowered when drug metabolism is stimulated by pretreatment with phenobarbital or butyl-hydroxyanisole (BHA). By contrast, administration of L-cysteine is synergistic with the antischistosomal effect of oltipraz. Evaluation of a limited number of oltipraz analogs revealed among dithiolthiones rather stringent structural requirements for antischistosomal activity.