Author | Silva, Cristiane França da | |
Author | Batista, Denise da Gama Jaen | |
Author | Oliveira, Gabriel Melo | |
Author | Souza, Elen Mello de | |
Author | Hammer, Erica Ripoll | |
Author | Silva, Patricia Bernardino da | |
Author | Daliry, Anissa | |
Author | Araujo, Julianna Siciliano | |
Author | Britto, Constança | |
Author | Rodrigues, Ana Carolina Mondaine | |
Author | Liu, Zongying | |
Author | Farahat, Abdelbasset A. | |
Author | Kumar, Arvind | |
Author | Boykin, David W. | |
Author | Soeiro, Maria de Nazaré Correia | |
Access date | 2016-09-27T13:26:45Z | |
Available date | 2016-09-27T13:26:45Z | |
Document date | 2012 | |
Citation | SILVA, Cristiane França da; et al. In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - against Trypanosoma cruzi Infection. PLoS One, v.7, n.1, e30356, 8p, Jan. 2012. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/15959 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Arylimidamides | pt_BR |
Subject in Portuguese | Tratamento | pt_BR |
Title | In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection | pt_BR |
Type | Article | |
DOI | 10.1371/journal.pone.0030356 | |
Abstract | Chagas disease is caused by infection with the intracellular protozoan parasite Trypanosoma cruzi. At present, nifurtimox and benznidazole, both compounds developed empirically over four decades ago, represent the chemotherapeutic arsenal for treating this highly neglected disease. However, both drugs present variable efficacy depending on the geographical area and the occurrence of natural resistance, and are poorly effective against the later chronic stage. As a part of a search for new therapeutic opportunities to treat chagasic patients, pre-clinical studies were performed to characterize the activity of a novel arylimidamide (AIA--DB1831 (hydrochloride salt) and DB1965 (mesylate salt)) against T. cruzi. These AIAs displayed a high trypanocidal effect in vitro against both relevant forms in mammalian hosts, exhibiting a high selectivity index and a very high efficacy (IC(50) value/48 h of 5-40 nM) against intracellular parasites. DB1965 shows high activity in vivo in acute experimental models (mouse) of T. cruzi, showing a similar effect to benznidazole (Bz) when compared under a scheme of 10 daily consecutive doses with 12.5 mg/kg. Although no parasitological cure was observed after treating with 20 daily consecutive doses, a combined dosage of DB1965 (5 mg/kg) with Bz (50 mg/kg) resulted in parasitaemia clearance and 100% animal survival. In summary, our present data confirmed that aryimidamides represent promising new chemical entities against T. cruzi in therapeutic schemes using the AIA alone or in combination with other drugs, like benznidazole. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | aryimidamides | pt_BR |
Subject | Therapeutic | pt_BR |
xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |