In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

Drug Des Devel Ther. 2013 Nov 15;7:1377-84. doi: 10.2147/DDDT.S51298. eCollection 2013.

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.

Keywords: Plasmodium falciparum; antimalarial studies; cross-resistance; stage-specificity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / pharmacokinetics
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacokinetics
  • Artemisinins / pharmacology
  • Artesunate
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Female
  • Half-Life
  • Malaria / drug therapy
  • Malaria / parasitology
  • Mice
  • Oxazines / administration & dosage
  • Oxazines / pharmacokinetics
  • Oxazines / pharmacology*
  • Plasmodium berghei / drug effects*
  • Plasmodium falciparum / drug effects*
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology*

Substances

  • Antimalarials
  • Artemisinins
  • Oxazines
  • Pyridines
  • SSJ 183
  • Artesunate