S-Substituted glutathiones were prepared and investigated as inhibitors of the enzyme, glyoxalase I. A non-polar region exists on the enzyme and plays an important role in the formation of an enzyme-inhibitor complex. The amount of inhibition of glyoxalaseincreases as the alkyl chain is lengthened frommethyl to n-octyl. Several S-arylglutathiones were also prepared in orderto take advantage of this nonpolar region on the enzyme. For example, S-(p-bromobenzyl) glutathione (14) gave about 920-fold better binding than the previously reported S-methylglutathione (1).

It has recently been shown that S-alkylglutathiones are potent competitive inhibitors of glyoxalase. 3 The glyoxalase system (glyoxalase I and glyoxalase II) is present in plant and animal cells and converts methyl-glyoxal into lactic acid. Since methylglyoxal and other-ketoaldehydes are known to be carcinostatic agents, 4 it was suggested that inhibitors of the glyoxalase system