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Overview
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Background
S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives have been proposed as possible anticancer agents, because of their ability to strongly inhibit the methylglyoxal-detoxifying enzyme glyoxalase I. Glyoxalase I inhibitor is a potent inhibitor of glyoxalase I.
In vitro: As a tumor-selective anticancer agent, Glyoxalase I inhibitor [3(Et)2] was evaluated against B16 melanotic melanoma, L1210 murine leukemia, and nonproliferating murine splenic lymphocytes in culture. The diethyl ester prodrugs of Glyoxalase I inhibitor [3(Et)2] also displayed significant tumour-selective toxicity towards L1210 cells compared with normal murine splenic lymphocytes in vitro [1].
In vivo: Small-scale efficacy studies indicated that 3b(Et)2 could effectively inhibit tumour growth in plasma esterase-deficient mice bearing murine B16 melanoma and in esterasedeficient athymic nude mice bearing androgen-independent human prostate PC-3 tumours or human colon HT-29 tumours [2].
Clinical trial: No clinical data are available.[1] Kavarana MJ, Kovaleva EG, Creighton DJ, Wollman MB, Eiseman JL. Mechanism-based competitive inhibitors of glyoxalase I: intracellular delivery, in vitro antitumor activities, and stabilities in human serum and mouse serum. J Med Chem. 1999;42(2):221-8.
[2] Creighton DJ, Zheng ZB, Holewinski R, Hamilton DS, Eiseman JL. Glyoxalase I inhibitors in cancer chemotherapy. Biochem Soc Trans. 2003;31(Pt 6):1378-82.
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