INHIBITORY EFFECT OF CHLOROQUINE ON THE PEROXIDASE-ACTIVITY OF FERRIPROTOPORPHYRIN-IX

The effect of the antimalarial chloroquine -4-[4-(diethylamino)-1-meth ylbutylamino]quinoline} on the oxidation of 2,2'-azinobis(3-ethylbenzo thiazoiine-6-sulfonate) (abts) promoted by ferriprotoporphyrin IX 8,13 -divinylporphyrin-2,18-dipropanoato)iron(III)] and H2O2 was studied. U nder the conditions [abts] much greater than [H2O2] much greater than [catalyst], the kinetic results showed a first-order dependence on bot h the peroxide (up to 8 x 10(-3) mol dm(-3)) and the catalyst concentr ation (up to 4 x 10(-6) mol dm(-3)), although a saturation effect was observed at higher concentrations. The values of the apparent second-o rder rate constants in the absence and presence of chloroquine were (1 .71 +/- 0.05) x 10(5) and (1.23 +/- 0.04) x 10(5) dm(6) mol(2) s(-1) a t pH 6.86, 303.1 +/- 0.2 K, and I = 0.10 mol dm(3) NaCl. Therefore, th e antimalarial inhibits the peroxidase activity by about 28% due the f ormation of a catalytically inactive complex with the haem. A first-or der dependence on the concentration of abts was also verified, followe d by a zero-order dependence at concentrations higher than 5 x 10(-3) mol dm(3). Some EPR spin-trapping experiments. and comparative studies in the presence of bromide ions. provided evidence for the participat ion of analogues of the horseradish peroxidase compounds I and II rath er than hydroxyl radicals, in the peroxidase activity of the haem. The results are discussed in the context of the antimalarial activity of chloroquine.