title: Plasmodium vivax: in vitro susceptibility of blood stages to synthetic trioxolane compounds and the diamidine DB75.
abstract: Plasmodium vivax is an important human pathogen causing malaria in more temperate climates of the world. Similar to Plasmodium falciparum, the causative agent for malaria tropica, drug resistance is beginning to emerge for this parasite species and this hampers adequate treatment of infection. We have used a short-term ex vivo drug assay to monitor activity of OZ277 (RBx-11160), a fully synthetic anti-malarial peroxide, and the diamidine DB75 against P. vivax. For both compounds as well as the anti-malarial reference compounds artesunate, artemether, and chloroquine, the in vitro IC(50) values were determined in one-cycle hypoxanthine incorporation assays. Results from such assays were found to be very similar compared to IC(50) values obtained from one-cycle P. falciparum hypoxanthine assays. We demonstrate the anti-parasite activity of OZ277 and the reference compounds to be faster than that of DB75. These data warrant clinical testing of OZ277 against P. vivax malaria and support recent data on clinical activity against P. vivax for DB75.
authors.affiliation: Biomedical Primate Research Centre, Department of Parasitology, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands.
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.forename: Annemarie
authors.initials: A
authors.lastname: van der Wel
authors.forename: Sarah
authors.initials: S
authors.lastname: Arbe-Barnes
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D016645:Aotidae; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D001550:Benzamidines / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D010545:Peroxides / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D010966:Plasmodium vivax / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D001550:Benzamidines; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D012717:Sesquiterpenes; D013141:Spiro Compounds; C489136:arterolane; D000077332:Artesunate; C033286:furamidine; D002738:Chloroquine; D000077549:Artemether