| Registro completo |
| Provedor de dados: |
J. Venom. Anim. Toxins incl. Trop. Dis.
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| País: |
Brazil
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| Título: |
Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
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| Autores: |
Ferreira,Daiane Dias
Mesquita,Juliana Tonini
Silva,Thais Alves da Costa
Romanelli,Maiara Maria
Batista,Denise da Gama Jaen
Silva,Cristiane França da
Gama,Aline Nefertiti Silva da
Neves,Bruno Junior
Melo-Filho,Cleber Camilo
Soeiro,Maria de Nazare Correia
Andrade,Carolina Horta
Tempone,Andre Gustavo
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| Data: |
2018-01-01
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| Ano: |
2018
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| Palavras-chave: |
Trypanosoma cruzi
Drug
Treatment
Sertraline
Drug repurposing
Drug repositioning
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| Resumo: |
Abstract Background: Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. Methods: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 μM, and activity against bloodstream trypomastigotes, with IC50 of 14 μM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. Conclusions: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.
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| Tipo: |
Info:eu-repo/semantics/article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992018000100321
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| Editor: |
Centro de Estudos de Venenos e Animais Peçonhentos
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| Relação: |
10.1186/s40409-018-0165-8
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| Formato: |
text/html
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| Fonte: |
Journal of Venomous Animals and Toxins including Tropical Diseases v.24 2018
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| Direitos: |
info:eu-repo/semantics/openAccess
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