title: Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties.
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.
authors.affiliation: Center for Neglected Diseases Drug Discovery, Institut Pasteur Korea, Bundang-gu, Seongnam-Si, Gyeonggi-do, South Korea.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Moraes
authors.affiliation: Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: White
authors.affiliation: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Braillard
authors.affiliation: Murdoch University, Murdoch, WA, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Perez
authors.affiliation: Center for Neglected Diseases Drug Discovery, Institut Pasteur Korea, Bundang-gu, Seongnam-Si, Gyeonggi-do, South Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Goo
authors.affiliation: Center for Neglected Diseases Drug Discovery, Institut Pasteur Korea, Bundang-gu, Seongnam-Si, Gyeonggi-do, South Korea Faculdade de Farmácia e Instituto de Biologia Molecular Celular da Universidade do Porto, Porto, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Gaspar
authors.affiliation: Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Shackleford
authors.affiliation: Faculdade de Farmácia e Instituto de Biologia Molecular Celular da Universidade do Porto, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.affiliation: Murdoch University, Murdoch, WA, Australia.
authors.forename: R C Andrew
authors.initials: RC
authors.lastname: Thompson
authors.affiliation: Center for Neglected Diseases Drug Discovery, Institut Pasteur Korea, Bundang-gu, Seongnam-Si, Gyeonggi-do, South Korea.
authors.forename: Lucio
authors.initials: L
authors.lastname: Freitas-Junior
authors.affiliation: Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria, Australia.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.affiliation: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland echatelain@dndi.org.
authors.forename: Eric
authors.initials: E
authors.lastname: Chatelain
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009547:Nifurtimox / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D014344:Trypanocidal Agents; D009547:Nifurtimox
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