Stereoselective S-oxygenation of an aryl-trifluoromethyl sulfoxide to the corresponding sulfone by rat liver cytochromes P450

Toltrazuril sulfoxide (TZR.SO) is the metabolite of the antiparasitic drug toltrazuril (TZR; 1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl-1,3,5,-triazine-2,4,6(1 H,3 H,5 H)-trione). The results of the present paper demonstrate that TZR.SO was metabolized by rat liver microsomes to the corresponding sulfone (TZR.SO 2). The reaction was mediated almost exclusively by different cytochromes P450, the most active being cytochromes P450 3A. TZR.SO exists as a racemic mixture; when each enantiomer was incubated separately in the presence of untreated rat liver microsomes, a 7.3-fold difference in the rate of S-oxygenation was found, indicating a marked substrate enantioselectivity for the reaction.