title: In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models.
abstract: The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schleiferböck
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Masataka
authors.initials: M
authors.lastname: Ihara
authors.forename: Isamu
authors.initials: I
authors.lastname: Itoh
authors.forename: Ian
authors.initials: I
authors.lastname: Bathurst
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Burrows
authors.forename: Pascal
authors.initials: P
authors.lastname: Fantauzzi
authors.forename: Julie
authors.initials: J
authors.lastname: Lotharius
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.forename: Julia
authors.initials: J
authors.lastname: Morizzi
authors.forename: David M
authors.initials: DM
authors.lastname: Shackleford
authors.forename: Karen L
authors.initials: KL
authors.lastname: White
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D037621:Artemisinins / Q000493:pharmacokinetics / Q000494:pharmacology; D000077332:Artesunate; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006207:Half-Life; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D010078:Oxazines; D011725:Pyridines; C561763:SSJ 183; D000077332:Artesunate
keywords: Plasmodium falciparum; antimalarial studies; cross-resistance; stage-specificity