title: Differential in vitro activities of ionophore compounds against Plasmodium falciparum and mammalian cells.
abstract: Twenty-two ionophore compounds were screened for their antimalarial activities. They consisted of true ionophores (mobile carriers) and channel-forming quasi-ionophores with different ionic specificities. Eleven of the compounds were found to be extremely efficient inhibitors of Plasmodium falciparum growth in vitro, with 50% inhibitory concentrations of less than 10 ng/ml. Gramicidin D was the most active compound tested, with 50% inhibitory concentration of 0.035 ng/ml. Compounds with identical ionic specificities generally had similar levels of antimalarial activity, and ionophores specific to monovalent cations were the most active. Compounds were further tested to determine their in vitro toxicities against mammalian lymphoblast and macrophage cell lines. Nine of the 22 compounds, i.e., alborixin, lonomycin, nigericin, narasin, monensin and its methylated derivative, lasalocid and its bromo derivative, and gramicidin D, most specific to monovalent cations, were at least 35-fold more active in vitro against P. falciparum than against the two other mammalian cell lines. The enhanced ability to penetrate the erythrocyte membrane after infection could be a factor that determines ionophore selectivity for infected erythrocytes.
authors.affiliation: Dynamique Moléculaire des Interactions Membranaires, Université Montpellier II, France.
authors.forename: C
authors.initials: C
authors.lastname: Gumila
authors.forename: M L
authors.initials: ML
authors.lastname: Ancelin
authors.forename: G
authors.initials: G
authors.lastname: Jeminet
authors.forename: A M
authors.initials: AM
authors.lastname: Delort
authors.forename: G
authors.initials: G
authors.lastname: Miquel
authors.forename: H J
authors.initials: HJ
authors.lastname: Vial
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics
chemical_list: D007476:Ionophores