Antimalarial activity in vitro of the glyoxalase I inhibitor diester, S-p-bromobenzylglutathione diethyl ester.
S-p-Bromobenzylglutathione diethyl ester induced toxicity in the malarial parasite Plasmodium falciparum in infected human red blood cells in culture. The median inhibitory concentration, IC50, was 4.77 +/- 0.12 microM (N = 10) for incorporation of [3H]hypoxanthine in nucleotide synthesis and 5.20 +/- 0.1 microM (N = 10) for incorporation of [14C]isoleucine into protein. The prospective mechanism of action is inhibition of glyoxalase I by the de-esterified metabolite, S-p-bromobenzylglutathione, and accumulation of the cytotoxic substrate methylglyoxal.
Thornalley
P J
PJ
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Strath
M
M
Wilson
R J
RJ
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D009711:Nucleotides / Q000096:biosynthesis; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis; D011765:Pyruvaldehyde / Q000378:metabolism; D014316:Tritium
D000962:Antimalarials; D002250:Carbon Radioisotopes; D009711:Nucleotides; D014316:Tritium; C085722:S-4-bromobenzylglutathione diethyl ester; C020233:S-(4-bromobenzyl)glutathione; D011765:Pyruvaldehyde; C083627:glutathione diethyl ester; D007791:Lactoylglutathione Lyase; D005978:Glutathione