S-(N-aryl-N-hydroxycarbamoyl)glutathione derivatives are tight-binding inhibitors of glyoxalase I and slow substrates for glyoxalase II.
Basic Information
ID: ALA1127571
Journal: J Med Chem
Title: S-(N-aryl-N-hydroxycarbamoyl)glutathione derivatives are tight-binding inhibitors of glyoxalase I and slow substrates for glyoxalase II.
Authors: Murthy NS, Bakeris T, Kavarana MJ, Hamilton DS, Lan Y, Creighton DJ.
Abstract: S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives are powerful competitive inhibitors of the anticancer target enzyme glyoxalase I. Indeed, the N-p-bromophenyl derivative is the strongest inhibitor of the enzyme from human erythrocytes yet reported (Ki = 1.4 x 10(-8) M). Structure-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) intermediate associated with the glyoxalase I reaction. The derivatives also 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.
CiteXplore: 8035422
DOI: 10.1021/jm00040a007
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