ANTIMALARIAL ACTIVITY IN-VITRO OF THE GLYOXALASE-I INHIBITOR DIESTER,S-P-BROMOBENZYLGLUTATHIONE DIETHYL ESTER

S-p-Bromobenzylglutathione diethyl ester induced toxicity in the malar ial parasite Plasmodium falciparum in infected human red blood cells i n culture, The median inhibitory concentration, IC50 was 4.77 +/- 0.12 mu M (N = 10) for incorporation of [H-3]hypoxanthine in nucleotide sy nthesis and 5.20 +/- 0.1 mu M (N = 10) for incorporation of [C-14]isol eucine into protein. The prospective mechanism of action is inhibition of glyoxalase I by the de-esterified metabolite, S-p-bromobenzylgluta thione, and accumulation of the cytotoxic substrate methylglyoxal.