Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17995
Title: Nelfinavir and lopinavir impair Trypanosoma cruzi trypomastigote infection in mammalian host cells and show anti-amastigote activity
Authors: Sangenito, Leandro S.
d`Avila-Levy, Claudia M.
Branquinha, Marta H.
Santos, André L. S.
Affilliation: Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.
Abstract: There is an urgent need to implement new strategies and to search for new chemotherapeutic targets to combat Chagas' disease. In this context, repositioning of clinically approved drugs appears as a viable tool to combat this and several other neglected pathologies. An example is the use of aspartic peptidase inhibitors (PIs) currently applied in human immunodeficiency virus (HIV) treatment against different infectious agents. Therefore, the main objective of this work was to verify the effects of the HIV-PIs nelfinavir and lopinavir against Trypanosoma cruzi using in vitro models of infection. Cytotoxicity assays with LLC-MK2 epithelial cells and RAW macrophages allowed an evaluation of the effects of HIV-PIs on the interaction between trypomastigotes and these cells as well as the survival of intracellular amastigotes. Pre-treatment of trypomastigotes with nelfinavir and lopinavir inhibited the association index with LLC-MK2 cells and RAW macrophages in a dose- and time-dependent manner. In addition, nelfinavir and lopinavir also significantly reduced the number of intracellular amastigotes in both mammalian cell lineages, particularly when administered in daily doses. Both compounds had no effect on nitric oxide production in infected RAW macrophages. These results open the possibility for the use of HIV-PIs as a tangible alternative in the treatment of Chagas' disease. However, the main mechanism of action of nelfinavir and lopinavir has yet to be elucidated, and more studies using in vivo models must be conducted.
Keywords: Trypanosoma cruzi
HIV-PI
Nelfinavir
Lopinavir
Chagas disease
keywords: Trypanosoma cruzi
Nelfinavir
Lopinavir
Doença de Chagas
Issue Date: 2016
Publisher: Elsevier
Citation: SANGENITO, Leandro S. et al. Nelfinavir and lopinavir impair Trypanosoma cruzi trypomastigote infection in mammalian host cells and show anti-amastigote activity. International Journal of Antimicrobial Agents, v.48, n.6, p.703-711, Dec. 2016.
DOI: 10.1016/j.ijantimicag.2016.09.017
ISSN: 0924-8579
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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