SACCHARIDE ANIONS AS INHIBITORS OF THE MALARIA PARASITE

The asexual erythrocytic stage of Plasmodium falciparum was grown in c ulture in the presence or absence of glycoconjugate polyanions of vary ing structure, size and substitutions. Heparin, dextran sulfate, fucoi dan and pentosan polysulfate had antimalarial IC50 values between one and 11 mu g ml(-1). Constituent heparin disaccharides were ineffective against the malaria parasite and desulfation from either the O- or N- substitution sites of heparin or reduction of the uronic acid carboxyl group neutralized the antimalarial response to varying degrees. Immob ilization of heparin onto agarose beads still permitted antimalarial a ctivity suggesting that parasite uptake of the glycoconjugate is not r equired for inhibition. Accordingly, it is concluded that invasion of free parasites into the erythrocytes was inhibited rather than parasit e maturation within the red cell. Merozoite surface antigen-1 was appa rently prevented from binding to human erythrocytes in the presence of highly sulfated polyanions and, in a dose-dependent fashion, heparin.