ELECTROCHEMICAL EVIDENCE OF A POSSIBLE ROUTE FOR THE METABOLISM OF OLTIPRAZ 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOLE-3-THIONE

The presence of the 5-pyrazinyl substituent induces some noticeable changes in the reaction pathways accompanying the electrochemical reduction of oltipraz compared with the behavior of dithiole-thiones, which do not possess such a substituent and are not endowed with antischistosomal activity. First, electrochemical techniques ascertain the transient formation of the radical anion resulting from the reversible addition of one electron to oltipraz in aprotic media. Second, the electrochemical two-electron reduction, under anaerobic conditions, yields a mixture of dianionic isomers which can be protonated one, two, and even three times. In the protonated species which also exist in isomeric forms and are not starting materials for the regeneration of oltipraz through oxidation, both the dithiole-thione and pyrazinyl rings are reduced. In the presence of air or methylating reagent, the two-electron reduction products are transformed into pyrrolo left bracket 1,2-a right bracket pyrazine derivatives, which are some of the major metabolites of oltipraz.