POTENTIATION OF AN ANTIMALARIAL OXIDANT DRUG

In a previous report we described the synergistic antimalarial interac tion between two structurally similar compounds, rufigallol and exifon e, To explain this phenomenon, we proposed that exifone is transformed inside the parasitized erythrocyte into a xanthone with potent antima larial properties. We speculated that the transformation process was i nduced by the prooxidant activity of rufigallol. On the basis of this model we hypothesized that exifone would act synergistically with othe r oxidant drugs, In the present study we have found a similar synergis tic interaction between exifone and ascorbic acid (vitamin C) against both chloroquine-susceptible and multidrug-resistant strains of Plasmo dium falciparum. The prooxidant activity of ascorbic acid against Plas modium-infected erythrocytes is believed to result from an intraerythr ocytic Fenton reaction occurring in the acidic food vacuole of the par asite. The hydroxyl radicals produced during this process are believed to attack exifone, which undergoes cyclodehydration to become 2,3,4,5 ,6-pentahydroxyxanthone (X5). Evidence presented to support this ''xan thone hypothesis'' includes the demonstration that the exifone double right arrow X5 transformation occurs readily in vitro under mildly aci dic conditions in the presence of iron, ascorbic acid, and oxygen.