Inhibition of proliferation of human leukaemia 60 cells by diethyl esters of glyoxalase inhibitors in vitro.
Diethyl esters of the glutathione S-conjugate S-p-bromobenzylglutathione, an inhibitor of glyoxalase I, and S-p-nitrobenzoxycarbonylglutathione, an inhibitor of glyoxalase II, induced growth arrest and toxicity in human leukaemia 60 cells in culture. The median growth inhibitory concentration IC50 values were 8.3 microM (95% C.I. 7.0-9.9 microM) for S-p-bromobenzylglutathione diethyl ester and 56 microM (95% C.I. 36-86 microM) for p-nitrobenzoxycarbonylglutathione. Monoethyl ester and unesterified derivatives were inactive. The diethyl ester derivatives were also toxic to mature human neutrophils under the same culture conditions where the respective median toxic concentration IC50 values were 39.7 (95% C.I. 35.4-44.5 microM) and 127 (95% C.I. 123-132 microM) microM. Diester derivatives may be of future interest in studying the cytotoxicity of glutathione S-conjugates and for the development of cytotoxic anti-tumour agents.
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Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Thornalley
P J
PJ
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000099301:Hydroxyacylglutathione Hydrolase
D004952:Esters; D005978:Glutathione; D005982:Glutathione Transferase; D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C020233:S-(4-bromobenzyl)glutathione