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Evaluation of methylene blue, pyrimethamine and its combination on an in vitro Neospora caninum model

Published online by Cambridge University Press:  11 January 2017

LUIZ MIGUEL PEREIRA ,
ISABEL CRISTINA VIGATO-FERREIRA ,
GABRIELA DE LUCA ,
CÁSSIA MARIANA BRONZON DA COSTA  and
ANA PATRÍCIA YATSUDA
LUIZ MIGUEL PEREIRA
Affiliation:
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil Núcleo de Apoio à Pesquisa em Produtos Naturais e Sintéticos, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
ISABEL CRISTINA VIGATO-FERREIRA
Affiliation:
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil Núcleo de Apoio à Pesquisa em Produtos Naturais e Sintéticos, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
GABRIELA DE LUCA
Affiliation:
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil
CÁSSIA MARIANA BRONZON DA COSTA
Affiliation:
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil
ANA PATRÍCIA YATSUDA*
Affiliation:
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil Núcleo de Apoio à Pesquisa em Produtos Naturais e Sintéticos, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
*
*Corresponding author: Departamento de Análises Clínicas, Bromatológicas e Toxicológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 14040-903, Brazil. E-mail: ayatsuda@fcfrp.usp.br
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Summary

Neospora caninum is an apicomplexan parasite strongly related to reproductive problems in cattle. The neosporosis control is not well established and several fronts are under development, predominantly based on immune protection, immunomodulation and chemotherapy. The use of anti-malarial drugs as therapeutic sources has, in theory, considerable potential for any apicomplexan. Drugs such as methylene blue (MB) and pyrimethamine (Pyr) represent therapeutic options for malaria; thus, their use for neosporosis should be assessed. In this work, we tested the effects of MB and Pyr on N. caninum proliferation and clearance, using LacZ-tagged tachyzoites. The drugs inhibited at nanomolar dosages and its combination demonstrated an antagonistic interaction in proliferation assays, according to the Chou and Talalay method for drug combination index. However, the drug combination significantly improved the parasite in vitro clearance. The repositioning of well-established drugs opens a short-term strategy to obtain low-cost therapeutics approaches against neosporosis.

Keywords

Neospora caninummethylene bluepyrimethaminerepositioningdrug combination
Type
Research Article
Information
Parasitology , Volume 144 , Issue 6 , May 2017 , pp. 827 - 833
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Copyright
Copyright © Cambridge University Press 2017 

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