Lapachol inhibition of alpha-ketoaldehyde metabolism

Lapachol and some of its derivatives have been reported to possess significant antitumour activity. Lapachol was found to be a linear competitive inhibitor of glyoxalase I from yeast, rat liver and human erythrocytes. The inhibition was fully reversible arguing against metal ion removal from glyoxalase I as the inhibition mechanism. Lapachol showed no reaction with glutathione or with a mixture of glutathione, methylglyoxal and their hemithiolacetal adduct. O-Methyl-lapachol did not inhibit yeast or rat liver glyoxalase I, while lawsone inhibited the yeast enzyme. Lapachol and lawsone inhibited sheep liver α-ketoaldehyde dehydrogenase non-competitively. No evidence was found that lapachol or its Fe(III) complex could nick DNA. No inhibition of ribonucleotide reductase by lapachol was observed. Thus the antineoplastic effects of lapachol and congeners could stem partially from α-ketoaldehyde metabolic blockade.