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In the course of our screening program to discover antimalarial antibiotics, which are active against drug resistant Plasmodium falciparum in vitro and rodents infected with P. berghei in vivo, from the culture broth of microorganisms, we found a selective and potent active substance produced by an actinomycete strain K99-0413. It was identified as a known polyether antibiotic, X-206. We also compared the in vitro antimalarial activities and cytotoxicities of 12 known polyethers with X-206. Among them, X-206 showed the most 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 play an important biological role for the intracellular growth of P. falciparum in parasitized erythrocytes. Moreover, X-206 showed potent in vivo antimalarial activity on the rodent model, though the therapeutic window was narrow compared with its selective toxicity in vitro. These observations are the first report of antimalarial activity of X-206.

Potent Antimalarial Activities of Polyether Antibiotic, X-206.