التفاصيل البيبلوغرافية
| العنوان: |
New insights into the pro-oxidant mechanism of dehydroleucodine on Trypanosoma cruzi. |
| المؤلفون: |
Gomez, Jessica, Coll, Mauro, Guarise, Carla, Cifuente, Diego, Masone, Diego, Tello, Paula Faral-, Piñeyro, María Dolores, Robello, Carlos, Reta, Guillermo, Sosa, Miguel Ángel, Barrera, Patricia |
| المصدر: |
Scientific Reports; 8/15/2024, Vol. 14 Issue 1, p1-14, 14p |
| مصطلحات موضوعية: |
TRYPANOSOMA cruzi, CHAGAS' disease, NEGLECTED diseases, DRUG target, MOLECULAR dynamics |
| مستخلص: |
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, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite. [ABSTRACT FROM AUTHOR] |
|
Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder