S-(N-ARYL-N-HYDROXYCARBAMOYL)GLUTATHIONE DERIVATIVES ARE TIGHT-BINDING INHIBITORS OF GLYOXALASE-I AND SLOW SUBSTRATES FOR GLYOXALASE-II

S-(N-Aryl-N-hydroxycarbamoyl) glutathione derivatives are powerful com petitive inhibitors of the anticancer target enzyme glyoxalase I. Inde ed, the N-p-bromophenyl derivative is the strongest inhibitor of the e nzyme from human erythrocytes yet reported (K-i = 1.4 x 10(-8) M). Str ucture-activity correlations indicate that the high affinities of the derivatives for both human and yeast glyoxalase I are due to the fact that the derivatives are hydrophobic analogs of the enediol(ate) inter mediate associated with the glyoxalase I reaction. The derivatives als o proved to be slow substrates for the thioester hydrolase glyoxalase II (bovine liver). Compounds of this type are of interest as potential tumor-selective anticancer agents, based on the abnormally low levels of glyoxalase II activity in some types of cancer cells.