| dc.creator | Alcazar, Wilmer | |
| dc.creator | Alakurti, Sami | |
| dc.creator | Padrón-Nieves, Maritza | |
| dc.creator | Tuonomen, Maija Liisa | |
| dc.creator | Rodríguez, Noris | |
| dc.creator | Yli-Kauhaluoma, Jari | |
| dc.creator | Ponte-Sucre, Alicia | |
| dc.date | 2021-06-24T19:56:06Z | |
| dc.date | 2021-06-24T19:56:06Z | |
| dc.date | 2021-06-24 | |
| dc.date.accessioned | 2022-10-28T01:40:06Z | |
| dc.date.available | 2022-10-28T01:40:06Z | |
| dc.identifier | 2076-2607 | |
| dc.identifier | http://hdl.handle.net/10872/21166 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4954547 | |
| dc.description | Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. Methods: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and
superoxide production by infected macrophages was determined. Results: From the tested 28 compounds,
those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active
(GI50 2 M, cytotoxic CC50 > 45 M, SI > 20) for the reference strain LTB0016 and for patient isolates.
The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05)
and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although
neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide
production in infected macrophages. Conclusion: Our results suggest that due to their efficacy and
selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis. | |
| dc.description | This research was funded by the Universidad Central de Venezuela Council for Research,
grants CDCH-UCV PI-09-8717-2013/1 (M.P.-N.) and PG-09-8646-2013/1 (A.P.-S.). This study also was supported by the Foundation for Research of Natural Resources in Finland, Marjatta ja Eino Kollin
Säätiö, the Academy of Finland (Projects 252308, 264020, 265481) and the COST Action CM-0801
(New drugs for neglected diseases). Finally, A.P.-S. is grateful for the support conferred by the Alexander von Humboldt Foundation and the Siebold-Collegium Institute for Advanced Studies, University of Würzburg, Germany. | |
| dc.language | en | |
| dc.relation | Microorganisms;9: 320, 2021. https://doi.org/10.3390/microorganisms9020320 | |
| dc.subject | Leishmania | |
| dc.subject | betulin derivatives | |
| dc.subject | plsma membrane potential | |
| dc.subject | mitochondrial membrane potential | |
| dc.subject | therapeutic failure | |
| dc.subject | drug resistance | |
| dc.title | Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production | |
| dc.type | Article | |
