Drug repurposing for Chagas disease: In vitro assessment of nimesulide against Trypanosoma cruzi and insights on its mechanisms of action

Chagas disease is a neglected illness caused by Trypanosoma cruzi and its treatment is done only with two drugs, nifurtimox and benznidazole. However, both drugs are ineffective in the chronic phase, in addition to causing serious side effects. This context of therapeutic limitation justifies the co...

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Bibliographic Details
Published in:PloS one 2021-10, Vol.16 (10), p.e0258292
Main Authors: Trindade, Joana D'Arc S, Freire-de-Lima, Célio Geraldo, Côrte-Real, Suzana, Decote-Ricardo, Debora, Freire de Lima, Marco Edilson
Format: Article
Language:English
Subjects:
Animals
Anti-inflammatory agents
Apoptosis
Benznidazole
Cell death
Cell Death - drug effects
Cell Survival - drug effects
Chagas disease
Chagas Disease - drug therapy
Chagas Disease - parasitology
Complications and side effects
Drug Repositioning
Drug therapy
Drugs
Ethanol
Health aspects
Infections
Inflammation
Laboratory animals
Life Cycle Stages - drug effects
Mice
Mice, Inbred BALB C
Molecular structure
Nifurtimox
Nimesulide
Nitrogen dioxide
Nonsteroidal anti-inflammatory drugs
Parasites
Parasites - drug effects
Parasitic diseases
Patient outcomes
Severe acute respiratory syndrome coronavirus 2
Side effects
Sulfonamides - chemistry
Sulfonamides - pharmacology
Sulfonamides - therapeutic use
Tropical diseases
Trypanosoma cruzi
Trypanosoma cruzi - drug effects
Trypanosoma cruzi - growth & development
Trypanosoma cruzi - physiology
Trypanosoma cruzi - ultrastructure
Vector-borne diseases
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Summary:Chagas disease is a neglected illness caused by Trypanosoma cruzi and its treatment is done only with two drugs, nifurtimox and benznidazole. However, both drugs are ineffective in the chronic phase, in addition to causing serious side effects. This context of therapeutic limitation justifies the continuous research for alternative drugs. Here, we study the in vitro trypanocidal effects of the non-steroidal anti-inflammatory drug nimesulide, a molecule that has in its chemical structure a toxicophoric nitroaromatic group (NO2). The set of results obtained in this work highlights the potential for repurposing nimesulide in the treatment of this disease that affects millions of people around the world.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0258292