Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28829 |
Resumo: | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil |
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Otta, Dayane AndriottiAraújo, Fernanda Fortes deRezende, Vítor Bortolo deFagundes, Elaine Maria SouzaSantos, Silvana Maria ElóiSilva, Matheus Fernandes CostaSantos, Raiany AraújoCosta, Heloísa AlvesSiqueira Neto, Jair LageMartins Filho, Olindo AssisCarvalho, Andréa Teixeira de2018-09-17T13:46:48Z2018-09-17T13:46:48Z2018OTTA, Dayane Andriotti et al. Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity. Antimicrob Agents Chemother., v. 62, n. 4, e01834-17, 20180066-4804https://www.arca.fiocruz.br/handle/icict/2882910.1128/AAC.01834-17engAmerican Society for MicrobiologyDoença de Chagasscreening compoundsTrypanosoma cruziChagas diseasescreening compoundsTrypanosoma cruziIdentification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilFundação 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, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrazilFundação 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, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilSkaggs School of Pharmacy and Pharmaceutical Sciences. University of California. San Diego, CA, USAFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, BrazilIn 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/28829/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALIdentification of Anti-Trypanosoma cruzi.pdfIdentification of Anti-Trypanosoma cruzi.pdfapplication/pdf1487359https://www.arca.fiocruz.br/bitstream/icict/28829/2/Identification%20of%20Anti-Trypanosoma%20cruzi.pdfc0c9e07911986f5f9b81e5c897c516a0MD52TEXTIdentification of Anti-Trypanosoma cruzi.pdf.txtIdentification of Anti-Trypanosoma cruzi.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| title |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| spellingShingle |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity Otta, Dayane Andriotti Doença de Chagas screening compounds Trypanosoma cruzi Chagas disease screening compounds Trypanosoma cruzi |
| title_short |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| title_full |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| title_fullStr |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| title_full_unstemmed |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| title_sort |
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity |
| author |
Otta, Dayane Andriotti |
| author_facet |
Otta, Dayane Andriotti Araújo, Fernanda Fortes de Rezende, Vítor 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 |
| author_role |
author |
| author2 |
Araújo, Fernanda Fortes de Rezende, Vítor 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 |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Otta, Dayane Andriotti Araújo, Fernanda Fortes de Rezende, Vítor 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 |
| dc.subject.other.pt_BR.fl_str_mv |
Doença de Chagas screening compounds Trypanosoma cruzi |
| topic |
Doença de Chagas screening compounds Trypanosoma cruzi Chagas disease screening compounds Trypanosoma cruzi |
| dc.subject.en.pt_BR.fl_str_mv |
Chagas disease screening compounds Trypanosoma cruzi |
| description |
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil |
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2018 |
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2018-09-17T13:46:48Z |
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2018-09-17T13:46:48Z |
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2018 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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 |
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https://www.arca.fiocruz.br/handle/icict/28829 |
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0066-4804 |
| dc.identifier.doi.none.fl_str_mv |
10.1128/AAC.01834-17 |
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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 0066-4804 10.1128/AAC.01834-17 |
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American Society for Microbiology |
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American Society for Microbiology |
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