title: In vitro activity of antimalarial compounds on the exoerythrocytic stages of Plasmodium cynomolgi and P. knowlesi.
abstract: Primary cultures of Macaca mulatta hepatocytes infected with sporozoites of Plasmodium knowlesi, P. cynomolgi (Cambodian strain), and P. cynomolgi bastianellii were exposed in vitro to 7 antimalarial compounds. The number of exoerythrocytic schizonts present after 4-7 days of culture was used to assess the activity. With pyrimethamine, proguanil, cycloguanil, primaquine, and 2 of its analogues (WR242511 and WR238605), marked inhibition of schizont formation could be achieved at concentrations below those causing a cytotoxic effect on the host hepatocytes. Chloroquine had only minimal schizonticidal activity at a concentration that produced severe hepatocyte toxicity. This simian in vitro system provides a reliable model for screening antimalarial compounds and for investigating their effects on the hepatic stage of malaria parasites.
authors.affiliation: Division of Parasitic Diseases, Center for Infectious Diseases, Atlanta, Georgia.
authors.forename: T L
authors.initials: TL
authors.lastname: Fisk
authors.forename: P
authors.initials: P
authors.lastname: Millet
authors.forename: W E
authors.initials: WE
authors.lastname: Collins
authors.forename: P
authors.initials: P
authors.lastname: Nguyen-Dinh
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000469:parasitology; D008253:Macaca mulatta; D010961:Plasmodium / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000962:Antimalarials