Polyvalent effect enhances diglycosidic antiplasmodial activity.

An efficient and facile total synthesis of diglycoside Matayoside D isolated from the root bark of Matayba guianensis with antiplasmodial activity have been accomplished in 11 steps with 5% overall yields starting from commercially available glucose and rhamnose. Furthermore, a class of the diglycosidic derivatives with different lengths of the linker and valences were also prepared and evaluated for their antiplasmodial activities against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Low valent and short linker attached diglycoside show no enhancement of the antiplasmodial activity while polyvalent conjugates showed enhanced antiplasmodial activity with IC50 value at least 20 fold better than that of the corresponding diglycosidic monomer. The polyvalent diglycoside were non-cytotoxic against normal mammalian cells under 50,000 μg/L.