Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
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2018
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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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Trypanosoma cruzi, Drug, Treatment, Sertraline, Drug repurposing, Drug repositioning
Citação
FERREIRA, Daiane Dias et al. Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study. Journal of Venomous Animals and Toxins Including Tropical Diseases, Botucatu, v. 24, p. 1-12, 2018. DOI: 10.1186/s40409-018-0165-8. Disponível em: https://www.scielo.br/j/jvatitd/a/gQm7Jfj7wFD6GTpdhhDKqkN/?lang=en. Acesso em: 8 nov. 2024.