- The Glyoxalase System - An introduction
- Chemotherapy of cancer by glyoxalase I inhibitors
The Glyoxalase System - An introduction
Dr Paul J. Thornalley.
Preface from Thornalley, P.J. (1993) The glyoxalase system in health and disease. Mol. Aspects of Med. 14, 287-371
Chemotherapy of cancer by glyoxalase I inhibitors
To study the development of glyoxalase I inhibitor diester prodrugs as antitumour agents.
Methylglyoxal is an endogenous mutagen that is detoxified in all cells by the glyoxalase system. Pharmacological inhibition of methylglyoxal detoxification by inhibitors of glyoxalase I induced an acute increase in methylglyoxal, DNA modification and induction of apoptosis. We developed a glyoxalase I inhibitor diester prodrug with potent antitumour activity in vitro and in vivo. We demonstrated that methylglyoxal and glyoxalase I inhibitors were selectively toxic to tumour cells in vitro and induced apoptosis.
First demonstration of antitumour activity in vitro by a glyoxalase I inhibitor glutathione-S-conjugate diester prodrug:
- Lo, T.W.C. and Thornalley, P.J. (1992) Inhibition of growth of human leukaemia 60 cells in culture by diethyl esters of glyoxalase inhibitors, Biochem. Pharmacol. 44, 2357-2363.
First demonstration of antitumour activity in vivo by a glyoxalase I inhibitor glutathione-S-conjugate diester prodrug:
- Thornalley, P.J., Wyatt, C., Davies, N., Edwards, L.G., Kang, Y., Ladan, M.J. and Double, J. (1996) Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo. Inhibition of glyoxalase I and induction of apoptosis. Biochem. Pharmacol. 51, 1365-1372.