Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties

Antimicrob Agents Chemother. 2015;59(6):3645-7. doi: 10.1128/AAC.05139-14. Epub 2015 Apr 6.

Abstract

With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their in vitro activity against a panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas disease; in vitro toxicity and absorption, distribution, metabolism, and excretion characteristics; and in vivo pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Disease / drug therapy
  • Chagas Disease / parasitology
  • Female
  • Humans
  • Male
  • Mice
  • Nifurtimox / chemistry*
  • Nifurtimox / pharmacokinetics*
  • Nifurtimox / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Trypanocidal Agents / adverse effects
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacokinetics*
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma cruzi / drug effects*

Substances

  • Trypanocidal Agents
  • Nifurtimox