Enantioselective binding of albendazole sulphoxide to cytosolic proteins from helminth parasites.

The pharmacological effect of the active albendazole metabolite, albendazole sulphoxide (ABZSO), depends on its sustained presence at the site of parasite location and its binding to helmith beta-tubulin. ABZSO is found in the plasma and tissues of albendazole-treated animals in two enantiomeric forms: (+)ABZSO and (-)ABZSO. Knowledge of enantioselectivity in drug action is necessary, since any difference in target proteins affinity between enantiomers may have implications on the pharmacological effect of this anthelmintic molecule. The binding of ABZSO to mammalian and helminth parasites cytosolic proteins, as well as the differential binding of both enantiomers, were studied. Cytosolic proteins from Moniezia expansa (cestode), Ascaris suum (nematode), Fasciola hepatica (trematode), rat liver and brain as well as purified porcine brain tubulin were used. Drug analysis was performed by HPLC using both C18 and chiral columns. ABZSO protein binding was quantitatively different between parasite species (4.17, 2.5 and 1.07 ng/mg for cestode, nematode and trematode, respectively); this binding to helminth cytosolic proteins was enantioselective. Enantiomeric ratios of (-)ABZSO/(+)ABZSO as a percentage were: 43/57 (Ascaris), 36/64 (Moniezia) and 91/9 (Fasciola). Conversely, the binding of ABZSO to mammalian cytosolic proteins showed no enantioselectivity. The overall binding affinity of ABZSO for mammalian cytosolic proteins was lower than that observed in helminth proteins. The characterization of the comparative binding pattern of ABZSO enantiomers to cytosolic proteins from helminth parasites and mammalian tissues may contribute to understanding the pharmacological properties of this chiral anthelmintic molecule.