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Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

Published online by Cambridge University Press:  23 September 2019

Matheus Marques Milagre ,
Renata Tupinambá Branquinho ,
Maira Fonseca Gonçalves ,
GMP de Assis ,
Maykon Tavares de Oliveira ,
LES Reis ,
Dênia Antunes Saúde-Guimarães  and
Marta de Lana Open the ORCID record for Marta de Lana [Opens in a new window]
Matheus Marques Milagre
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
Renata Tupinambá Branquinho
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
Maira Fonseca Gonçalves
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
GMP de Assis
Affiliation:
Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
Maykon Tavares de Oliveira
Affiliation:
Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
LES Reis
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
Dênia Antunes Saúde-Guimarães
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
Marta de Lana*
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil
*
Author for correspondence: Marta de Lana, E-mail: [email protected]
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Abstract

Background:

The current drugs for Chagas disease treatment present several limitations

Methods:

The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.

Results:

The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.

Conclusion:

GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.

Keywords

Goyazensolidein vitroin vivotoxicitytreatmentTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 147 , Issue 1 , January 2020 , pp. 108 - 119
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Copyright
Copyright © Cambridge University Press 2019

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