Olfa Chiboub1,2,3,4, Ines Sifaoui5,6,7, Manef Abderrabba8, Mondher Mejri8, José J Fernández9,10, Ana R Díaz-Marrero9, Jacob Lorenzo-Morales5,6,7, José E Piñero5,6,7. 1. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez S/N, 38203, La Laguna, Tenerife, Spain. olfachiboubt@gmail.com. 2. Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain. olfachiboubt@gmail.com. 3. Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez 2, 38206, La Laguna, Tenerife, Spain. olfachiboubt@gmail.com. 4. Laboratoire Matériaux-Molécules et Applications, University of Carthage, La Marsa, Carthage, Tunisia. olfachiboubt@gmail.com. 5. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez S/N, 38203, La Laguna, Tenerife, Spain. 6. Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain. 7. Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), Madrid, Spain. 8. Laboratoire Matériaux-Molécules et Applications, University of Carthage, La Marsa, Carthage, Tunisia. 9. Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez 2, 38206, La Laguna, Tenerife, Spain. 10. Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez S/N, 38203, La Laguna, Tenerife, Spain.
Abstract
BACKGROUND: The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells. METHODS: The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells. RESULTS: The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death. CONCLUSIONS: These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi.
BACKGROUND: The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells. METHODS: The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells. RESULTS: The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death. CONCLUSIONS: These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi.
Entities:
Keywords:
Antikinetoplastid; Apoptosis-like; Diterpenes; L. amazonensis; Marine compounds; T. cruzi
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