Paroxetine activity against Trypanosoma cruzi: in vitro and in vivo studies.
- 1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil.
- 2Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Estrutural, Rio de Janeiro, RJ, Brasil.
- 3Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET/Universidad Nacional de La Plata, Facultad de Ciencias Exactas, Laboratorio de Investigación y Desarrollo de Bioactivos, La Plata, Buenos Aires, Argentina.
Abstract
Background
Chagas disease (CD) lacks effective therapy. However, the long time and high financial investments for the development of new drugs are limiting obstacles. The repositioning of drugs is an interesting approach for novel antiparasitic medicines. Previous results suggest that paroxetine (PXT) may represent a promising anti-Trypanosoma cruzi agent.Objectives
Our aim was to evaluate the activity and cellular targets of PXT on T. cruzi infection in vitro and in vivo.Methods
PXT and benznidazole (BZ) were assayed against intracellular and bloodstream forms for different periods of incubation by colorimetric and light microscopy analysis. Bloodstream forms were exposed to PXT and observed by transmission electron microscopy. PXT alone and in combination with BZ was evaluated as an acute mouse model of T. cruzi infection.Findings
PXT is active (EC50 = 2.18 μM) against amastigotes of T. cruzi (Tulahuen-β gal strain), resulting in > 99% suppression of parasitism after 168 h of drug exposure. Upon bloodstream forms (Y strain), PXT was effective, displaying EC50 values of 8.90 and 4.27 μM after 2 and 24 h of incubation, respectively, revealing a rapid trypanocidal activity. PXT triggered ultrastructural alterations on trypomastigotes, including cytoplasmic disorganization, numerous contractile vacuoles besides damage on the mitochondria and paraflagellar stem. The proof of concept using a mouse model of acute T. cruzi infection demonstrates that although the parasitaemia was suppressed, PXT was unable to protect against mortality.Main conclusions
Our findings demonstrate the activity of PXT against T. cruzi and reinforces the relevance of drug repositioning for CD.
Related
- Optimization of an in vitro drug screening assay for anti-Trypanosoma cruzi activity using epimastigotes.
- First records of Triatoma sanguisuga (Hemiptera: Reduviidae) and detection of Trypanosoma cruzi (Trypanosomatida:Trypanosomatidae) in southern New Jersey, United States
- Trypanosoma cruzi cell atlas as a single-cell resource for understanding parasite population heterogeneity and differentiation
- A global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system
- A Single Enzyme Catalyses Formation of Trypanothione from Glutathione and Spermidine in Trypanosoma cruzi
BibTeX
@article{morais2026paroxetine,
title = {{Paroxetine activity against Trypanosoma cruzi: in vitro and in vivo studies.}},
author = {Gabriela Rodrigues Leite Morais and Denise da Gama Jaén Batista and Marcos Meuser Batista and Raquel Silva de Azevedo and Sandra Maria de Oliveira Souza and Alan Talevi and Lucas N Aberca and Maria de Nazaré Correia Soeiro},
journal = {Memorias do Instituto Oswaldo Cruz},
year = {2026},
month = oct,
doi = {10.1590/0074-02760260241},
url = {https://europepmc.org/article/MED/42912047},
note = {CC BY},
}
RIS
TY - JOUR
TI - Paroxetine activity against Trypanosoma cruzi: in vitro and in vivo studies.
AU - Gabriela Rodrigues Leite Morais
AU - Denise da Gama Jaén Batista
AU - Marcos Meuser Batista
AU - Raquel Silva de Azevedo
AU - Sandra Maria de Oliveira Souza
AU - Alan Talevi
AU - Lucas N Aberca
AU - Maria de Nazaré Correia Soeiro
PY - 2026
DA - 2026/10/16
JO - Memorias do Instituto Oswaldo Cruz
DO - 10.1590/0074-02760260241
UR - https://europepmc.org/article/MED/42912047
AB - Background Chagas disease (CD) lacks effective therapy. However, the long time and high financial investments for the development of new drugs are limiting obstacles. The repositioning of drugs is an interesting approach for novel antiparasitic medicines. Previous results suggest that paroxetine (PXT) may represent a promising anti-Trypanosoma cruzi agent.Objectives Our aim was to evaluate the activity and cellular targets of PXT on T. cruzi infection in vitro and in vivo.Methods PXT and benznidazole (BZ) were assayed against intracellular and bloodstream forms for different periods of incubation by colorimetric and light microscopy analysis. Bloodstream forms were exposed to PXT and observed by transmission electron microscopy. PXT alone and in combination with BZ was evaluated as an acute mouse model of T. cruzi infection.Findings PXT is active (EC50 = 2.18 μM) against amastigotes of T. cruzi (Tulahuen-β gal strain), resulting in > 99% suppression of parasitism after 168 h of drug exposure. Upon bloodstream forms (Y strain), PXT was effective, displaying EC50 values of 8.90 and 4.27 μM after 2 and 24 h of incubation, respectively, revealing a rapid trypanocidal activity. PXT triggered ultrastructural alterations on trypomastigotes, including cytoplasmic disorganization, numerous contractile vacuoles besides damage on the mitochondria and paraflagellar stem. The proof of concept using a mouse model of acute T. cruzi infection demonstrates that although the parasitaemia was suppressed, PXT was unable to protect against mortality.Main conclusions Our findings demonstrate the activity of PXT against T. cruzi and reinforces the relevance of drug repositioning for CD.
SN - 0074-0276
SN - 1678-8060
ER -