A panel of sulfated oligosaccharides was tested for antimalarial activity and inhibition of adhesion to the placental malaria receptor chondroitin-4-sulfate (CSA). The heparan sulfate mimetic PI-88, currently undergoing phase II anticancer trials, displayed the greatest in vitro antimalarial activity against Plasmodium falciparum (50% inhibitory concentration of 7.4 μM) and demonstrated modest adhesion inhibition to cell surface CSA.

Some of the severe pathophysiological symptoms of Plasmodium falciparum infection, the causative agent of the most lethal form of human malaria, involve carbohydrate interactions. For example, infected erythrocytes (IEs) can adhere to the glycosaminoglycans chondroitin-4-sulfate (CSA) and hyaluronic acid (6, 7, 14) in the placenta during pregnancy, and heparan sulfate may be involved in the formation of P. falciparum rosettes (5, 9, 10). Negatively charged polysaccharides, such as heparin, CSA, dextran sulfates, cellulose sulfates, fucoidan, and the nonsulfated glycosaminoglycan hyaluronic acid, have been shown experimentally to inhibit the in vitro invasion of P. falciparum merozoites into erythrocytes, block cytoadhesion of IEs to various host receptors (3, 11, 26), or disrupt P. falciparum rosettes (8, 24). In this study, we have examined a panel of sulfated oligosaccharides, including the heparan sulfate mimetic PI-88 (17), which is currently undergoing phase II clinical trials as an anticancer agent, both for their in vitro antimalarial activities and for their effects on adhesion to the host receptor CSA.