Author | Ferreira, Daiane Dias | |
Author | Mesquita, Juliana Tonini | |
Author | Silva, Thais Alves da Costa | |
Author | Romanelli, Maiara Maria | |
Author | Batista, Denise da Gama Jaen | |
Author | Silva, Cristiane França da | |
Author | Gama, Aline Nefertiti Silva da | |
Author | Neves, Bruno Junior | |
Author | Melo Filho, Cleber Camilo | |
Author | Soeiro, Maria de Nazare C. | |
Author | Andrade, Carolina Horta | |
Author | Tempone, Andre Gustavo | |
Access date | 2020-03-24T17:28:44Z | |
Available date | 2020-03-24T17:28:44Z | |
Document date | 2018 | |
Citation | 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 Disease, v. 24, n. 30, p. 1-12, 2018. | pt_BR |
ISSN | 1678-9199 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/40483 | |
Language | eng | pt_BR |
Publisher | BMC | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Droga | pt_BR |
Subject in Portuguese | Tratamento | pt_BR |
Subject in Portuguese | Sertralina | pt_BR |
Subject in Portuguese | Redefinição de drogas | pt_BR |
Subject in Portuguese | Reposicionamento de drogas | pt_BR |
Title | Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study | pt_BR |
Type | Article | pt_BR |
DOI | 10.1186/s40409-018-0165-8 | |
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. | pt_BR |
Affilliation | Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Goiás. Faculdade de Farmácia. Goiânia, GO, Brasil. | pt_BR |
Affilliation | Universidade Federal de Goiás. Faculdade de Farmácia. Goiânia, GO, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil. | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Drug | pt_BR |
Subject | Treatment | pt_BR |
Subject | Sertraline | pt_BR |
Subject | Drug repurposing | pt_BR |
Subject | Drug repositioning | pt_BR |