INHIBITION OF PROLIFERATION OF HUMAN LEUKEMIA 60 CELLS BY DIETHYL ESTERS OF GLYOXALASE INHIBITORS INVITRO

Diethyl esters of the glutathione S-conjugate S-p-bromobenzylglutathione, an inhibitor of glyoxalase 1, 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 muM (95% C.I. 7.0-9.9 muM) for S-p-bromobenzylglutathione diethyl ester and 56 muM (95% C.I. 36-86 muM) 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 muM) and 127 (95% C.I. 123-132 muM) muM. Diester derivatives may be of future interest in studying the cytotoxicity of glutathione S-conjugates and for the development of cytotoxic anti-tumour agents.