New insights into the pro-oxidant mechanism of dehydroleucodine on Trypanosoma cruzi.
Trypanosoma cruzi
Antiparasitic drug
Natural compound
Oxidative stress
Sesquiterpene lactone
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 08 2024
14 08 2024
Historique:
received:
09
02
2024
accepted:
01
08
2024
medline:
15
8
2024
pubmed:
15
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL,
Identifiants
pubmed: 39143185
doi: 10.1038/s41598-024-69201-0
pii: 10.1038/s41598-024-69201-0
doi:
Substances chimiques
Sesquiterpenes
0
Lactones
0
Reactive Oxygen Species
0
dehydroleucodine
36150-07-9
Trypanocidal Agents
0
Glutathione
GAN16C9B8O
Protozoan Proteins
0
trypanothione synthetase
EC 6.3.1.9
Amide Synthases
EC 6.3.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18875Informations de copyright
© 2024. The Author(s).
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