Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/28829
Title: Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity
Authors: Otta, Dayane Andriotti
Araújo, Fernanda Fortes de
Rezende, Vitor Bortolo de
Fagundes, Elaine Maria Souza
Santos, Silvana Maria Elói
Silva, Matheus Fernandes Costa
Santos, Raiany Araújo
Costa, Heloísa Alves
Siqueira Neto, Jair Lage
Martins Filho, Olindo Assis
Carvalho, Andréa Teixeira de
Affilliation: Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil/Universidade de Uberaba. Medicina Veterinária. Programa de Pós-graduação em Sanidade e Produção Animal nos Trópicos. Uberaba, Minas Gerais, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Skaggs School of Pharmacy and Pharmaceutical Sciences. University of California. San Diego, CA, USA
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil
Abstract: In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-Trypanosoma cruzi drug activity. This study aimed to identify the potential immunomodulatory activities of the anti-T. cruzi K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC50) of 71.0 mM (K777), 9.0 mM (PYR), and greater than 20 mM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-a1] CD81/CD41, gamma interferon-positive [IFN-g1] CD41/CD81 modulated by interleukin-10-positive [IL-101] CD41 T/CD81 T) than did PYR (TNF-a1 CD81, IL-101 CD81) and FUR (TNF-a1 CD81, IL-101 CD81). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.
Keywords: Chagas disease
screening compounds
Trypanosoma cruzi
keywords: Doença de Chagas
screening compounds
Trypanosoma cruzi
Issue Date: 2018
Publisher: American Society for Microbiology
Citation: OTTA, Dayane Andriotti et al. Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity. Antimicrob Agents Chemother., v. 62, n. 4, e01834-17, 2018
DOI: 10.1128/AAC.01834-17
ISSN: 0066-4804
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

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