Toxicity of "hydrophobic groupings" and the role of carbohydrates in Plasmodium falciparum infection.

We have tested various carbohydrate structures and neoglycoproteins (carbohydrate haptens attached to BSA) as inhibitors of the invasion of human red blood cells by Plasmodium falciparum merozoites (strain FCB) in synchronous in vitro cultures, using 3H-hypoxanthine incorporation into intraerythrocytic parasites as analytical tool, and have got the following results: The inhibition rate of N-acetyl-D-glucosamine glycosides is increased with increasing lipophilicity of the aglycon or spacer: CH3 less than (CH2)2NHCO(CH2)2COOCH3 less than (CH2)8COOCH3; p-Nitrophenyl glycosides proved to exhibit a toxic effect; The inhibition rate of synthetic disaccharide glycosides increased in the order beta DGal(1----4) beta DGlcNAcOCH3 less than beta DGlcNAc(1----4) beta DGlcNAcOCH3 less than beta DGlcNAc(1----4) alpha DManOCH3 less than beta DGlcNAc(1----4) beta DManO(CH2)8COOCH3; The O-linked tetrasaccharide alpha NeuAc(2----3) beta DGal(1----3) [alpha NeuAc(2----6)] alpha DGalNAcol, isolated from glycophorin A, was the best carbohydrate inhibitor tested so far; The inhibition rate of carbohydrates attached to BSA by an aliphatic spacer [-(CH2)8COOCH3] was not enhanced compared to the haptens; [DNP]33-BSA proved to be an extraordinary inhibitor of invasion which, however, most likely has to be attributed to a toxic effect; Observed toxicities appear to be attributable to hydrophobic interactions between the inhibitors and the RBC and merozoite membranes, which hampers both, intraerythrocytic growth of the parasite and its capability of RBC invasion.