DIFFERENTIAL IN-VITRO ACTIVITIES OF IONOPHORE COMPOUNDS AGAINST PLASMODIUM-FALCIPARUM AND MAMMALIAN-CELLS

Twenty-two ionophore compounds were screened for their antimalarial ac tivities. They consisted of true ionophores (mobile carriers) and chan nel-forming quasi-ionophores with different ionic specificities. Eleve n of the compounds were found to be extremely efficient inhibitors of Plasmodium falciparum growth in vitro,,vith 50% inhibitory concentrati ons of less than 10 ng/ml, Gramicidin D was the most active compound t ested, with 50% inhibitory concentration of 0.035 ng/ml, Compounds wit h identical ionic specificities generally had similar levels of antima larial activity, and ionophores specific to monovalent cations were th e most active, Compounds were further tested to determine their in vit ro toxicities against mammalian lymphoblast and macrophage cell lines. Nine of the 22 compounds, i.e., alborixin, lonomycin, nigericin, nara sin, monensin and its methylated derivative, lasalocid and its bromo d erivative, and gramicidin D, most specific to monovalent cations, were at least 35-fold more active in vitro against P. falciparum than agai nst the two other mammalian cell lines. The enhanced ability to penetr ate the erythrocyte membrane after infection could be a factor that de termines ionophore selectivity for infected erythrocytes.