SMALL-MOLECULE PROBES OF GLYOXALASE-I AND GLYOXALASE-II

A number of synthetic tropolones and hydrophobic S-blocked glutathione analogues were investigated as potential inhibitors of glyoxalase I f rom Saccharomyces cerevisiae and glyoxalase II from bovine liver. Seve ral tropolones containing a free C-2 hydroxy group were found to be po tent inhibitors of glyoxalase I, whereas the glutathione conjugates we re found to be modest to poor inhibitors of this enzyme. Most tropolon es and glutathione conjugates, except 5-p-tolylazotropolone and S-carb obenzoxy-L-glutathione, were found to be poor inhibitors of glyoxalase II. A recent report on an extremely active glyoxalase system from Pla smodium falciparum suggested that several of the more potent inhibitor s may have antimalarial properties. A number of these compounds in fac t, exhibited antimalarial activity in the low micromolar range. Furthe r studies are required to fully elucidate the mechanism(s) of the anti malarial properties of these compounds.