Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10056
Title: In Vitro and In Vivo Biological Effects of Novel Arylimidamide Derivatives against Trypanosoma cruzi
Authors: Timm, Bruno Lisboa
Silva, Patrícia Bernardino da
Batista, Marcos Meuser
Silva, Francisca Hildemagna Guedes da
Silva, Cristiane França da
Todwell, Richard R.
Patrick, Donald A.
Jones, Susan Kilgore
Bakunov, Stanislav A.
Bakunova, Svetlana M.
Soeiro, Maria de Nazaré C.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
University of North Carolina. Department of Pathology and Laboratory Medicine. Chapel Hill, North Carolina, USA.
University of North Carolina. Department of Pathology and Laboratory Medicine. Chapel Hill, North Carolina, USA.
University of North Carolina. Department of Pathology and Laboratory Medicine. Chapel Hill, North Carolina, USA.
University of North Carolina. Department of Pathology and Laboratory Medicine. Chapel Hill, North Carolina, USA.
University of North Carolina. Department of Pathology and Laboratory Medicine. Chapel Hill, North Carolina, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Abstract: Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, remains a serious public health problem in several Latin American countries. The available chemotherapies for CD have limited efficacy and exhibit undesirable side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad-spectrum activity against intracellular parasites, including T. cruzi. Therefore, our aim was to evaluate the biological activity of eight novel AIAs (16DAP002, 16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against experimental models of T. cruzi infection in vitro and in vivo. Our data show that none of the compounds induced a loss of cellular viability up to 32 M. Two AIAs, 18SAB075 and 16DAP002, exhibited good in vitro activity against different parasite strains (Y and Tulahuen) and against the two relevant forms of the parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075, this AIA was moved to in vivo tests for acute toxicity and parasite efficacy; nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed in the tests for parasite efficacy. In experimental models of acute T. cruzi infection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40% protection against mortality (at 5 mg/kg of body weight), being less effective than the reference drug, benznidazole.
Keywords: Chagas Disease
Tripanosoma Cruzi
Chemotherapy
In vitro
keywords: Doença de Chagas
Tripanosoma Cruzi
Quimioterapia
In vitro
DeCS: In vitro
Características dos Estudos
Issue Date: 2014
Publisher: American Society for Microbiology
Citation: TIMM, Bruno Lisboa et al. In Vitro and In Vivo Biological Effects of Novel Arylimidamide Derivatives against Trypanosoma cruzi. Antimicrobial Agents and Chemotherapy, v. 58, n.7, p. 3720-3726, Jul. 2014.
DOI: 10.1128/AAC.02353-14
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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