Fexinidazole : a potential new drug candidate for Chagas disease.

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dc.contributor.authorBahia, Maria Terezinha
dc.contributor.authorAndrade, Isabel Mayer de
dc.contributor.authorMartins, Tassiane Assíria Fontes
dc.contributor.authorNascimento, Álvaro Fernando da Silva do
dc.contributor.authorDiniz, Lívia de Figueiredo
dc.contributor.authorCaldas, Ivo Santana
dc.contributor.authorSilva, André Talvani Pedrosa da
dc.contributor.authorTrunz, Bernadette Bourdin
dc.contributor.authorTorreele, Els
dc.contributor.authorRibeiro, Isabela
dc.date.accessioned2014-12-16T23:28:18Z
dc.date.available2014-12-16T23:28:18Z
dc.date.issued2012
dc.description.abstractBackground: New safe and effective treatments for Chagas disease (CD) are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi. Methods and Findings: We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain), partially resistant (Y strain), and resistant (Colombian and VL-10 strains) to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure) through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses. Conclusions: Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazolesusceptible, partially resistant, and resistant T. cruzi. These findings illustrate the potential of fexinidazole as a drug candidate for the treatment of human CD.pt_BR
dc.identifier.citationBAHIA, M. T. et al. Fexinidazole : a potential new drug candidate for Chagas disease. PLoS Neglected Tropical Diseases, v. 6, p. e1870, 2012. Disponível em: <http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001870>. Acesso em: 08 nov. 2014.pt_BR
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0001870
dc.identifier.issn1932-6203
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/4178
dc.language.isoen_USpt_BR
dc.rights.licenseNenhuma autorização é necessária para depósito dos artigos publicados pelos Periódicos PloS em repositório. Fonte: Plos <http://www.plos.org/open-access/> Acesso em: 14 nov. 2014.pt_BR
dc.subjectChagas diseasept_BR
dc.subjectTrypanosoma cruzipt_BR
dc.titleFexinidazole : a potential new drug candidate for Chagas disease.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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