INHIBITION OF GROWTH OF HUMAN LEUKEMIA-60 CELLS BY S-2-HYDROXYACYLGLUTATHIONES AND MONOETHYL ESTER DERIVATIVES

S-2-Hydroxyacylglutathione derivatives were found to induce growth arrest and toxicity in human leukaemia 60 cells in culture. S-D-Lactoylglutathione was the most effective with a median inhibitory concentration IC50 of 82 muM (95% C.I. 65-105 muM). No similar toxicity was induced by reduced glutathione and/or the corresponding aldonic acid (500 muM) in human leukaemia 60 cells, nor by S-D-lactoylglutathione (500 muM) in mature human neutrophils under the same culture conditions. Monoethyl ester derivatives of the S-2-hydroxyacylglutathiones were prepared and also induced growth arrest and toxicity but were less effective than the corresponding unesterified compounds. S-2-Hydroxyacylglutathione derivatives also inhibited the incorporation of [H-3]thymidine into DNA early in the development of toxicity: for S-D-lactoylglutathione, the median inhibitory concentration was 74 muM (95% C.I. 47-116 muM). The mechanism of the inhibition of human leukaemia cell growth by S-D-lactoylglutathione and other S-2-hydroxyacylglutathione derivatives is unknown but appears to be mediated by the inhibition of DNA synthesis.