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  • Title: Sulfated cyclodextrins inhibit the entry of Plasmodium into red blood cells. Implications for malarial therapy.
    Author: Crandall IE, Szarek WA, Vlahakis JZ, Xu Y, Vohra R, Sui J, Kisilevsky R.
    Journal: Biochem Pharmacol; 2007 Mar 01; 73(5):632-42. PubMed ID: 17166484.
    Abstract:
    The effect of sulfated cyclodextrins on Plasmodium falciparum cultures was determined. alpha-, beta-, and gamma-Cyclodextrins having equal degrees of sulfation inhibited parasite viability to a similar degree, a result suggesting that the ring size of the cyclodextrin is not a critical factor for inhibitory activity. beta-Cyclodextrins containing fewer than two sulfate groups had no inhibitory activity, however, compounds containing 7-17 sulfates were found to be active in the microM range. Examination of treated cultures indicated that intracellular forms of the parasite were unaffected; however, increased numbers of extracellular merozoites were present. Active compounds produced enhanced erythrocyte staining with cationic dyes that could be reduced by stilbene disulfonates, a result suggesting that sulfated cyclodextrins inhibit parasite growth by interacting with the anion transport protein, AE1. Compounds that were found to be active in P. falciparum cultures were also found to inhibit P. berghei merozoite entry and could reduce the parasitemia of P. berghei infection in a mouse model, results suggesting that these compounds inhibit a common step in the merozoite invasion process of at least two Plasmodium species.
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