Potent antimalarial activities of polyether antibiotic, X-206

In the course of our screening program to discover antimalarial antibiotics , which are active against drug resistant Plasmodium falciparum in vitro an d rodents infected with P berghei in vivo, from the culture broth of microo rganisms, we found a selective and potent active substance produced by an a ctinomycete strain K99-0413. It was identified as a known polyether antibio tic, X-206. We also compared the in vitro antimalarial activities and cytot oxicities of 12 known polyethers with X-206. Among them, X-206 showed the m ost selective and potent inhibitory effect against both drug resistant and sensitive strains of P falciparum. Comparison of biological activities and ion-affinities of the above antibiotics suggests that monovalent cations pl ay an important biological role for the intracellular growth of P falciparu m in parasitized erythrocytes. Moreover, X-206 showed potent in vivo antima larial activity on the rodent model, though the therapeutic window was narr ow compared with its selective toxicity in vitro. These observations are th e first report of antimalarial activity of X-206.