| Author | Batista, Denise da Gama Jaén | |
| Author | Batista, Marcos Meuser | |
| Author | Oliveira, Gabriel Melo de | |
| Author | Amaral, Patrícia Borges do | |
| Author | Vieira, Joseli Lannes | |
| Author | Britto, Constança Carvalho | |
| Author | Junqueira, Angela | |
| Author | Lima, Marli Maria | |
| Author | Romanha, Álvaro José | |
| Author | Sales Junior, Policarpo Ademar | |
| Author | Stephens, Chad E. | |
| Author | Boykin, David W. | |
| Author | Soeiro, Maria de Nazaré Correia | |
| Access date | 2013-09-09T13:50:08Z | |
| Available date | 2013-09-09T13:50:08Z | |
| Document date | 2010 | |
| Citation | BATISTA, Denise da Gama Jaen et al. Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas’ Disease Treatment. Antimicrob Agents Chemother, v. 54, n. 7, p. 2940–2952, 2010. | pt_BR |
| ISSN | 0066-4804 | |
| URI | https://www.arca.fiocruz.br/handle/icict/6855 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | restricted access | |
| Title | Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas’ Disease Treatment | pt_BR |
| Type | Article | |
| DOI | 10.1128/AAC.01617-09 | pt_BR |
| Abstract | Chagas’ disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite Trypanosoma cruzi. The goal of this work is to investigate the in vitro andin vivo effects of the arylimidamide (AIA) DB766 against T. cruzi. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC50 s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively.
DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activityin vitro than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiactissue and presents efficacy similar to that of benznidazole in mouse models of T. Cruzii nfection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas’ disease treatment. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitárias. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Eco-epidemiologia da doença de Chagas. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Augusta State University. Department of Chemistry and Physics. Augusta, Georgia, USA. | pt_BR |
| Affilliation | Augusta State University.Department of Chemistry. Augusta, Georgia, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brazil. | pt_BR |
| Subject | Chagas Disease | pt_BR |
