Saber UCV
Repositorio Institucional
Repositorio Institucional
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https://saber.ucv.ve/handle/10872/4389
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| Title: | In Vitro Anti-Trypanosoma cruzi Activity of Dronedarone, a Novel Amiodarone Derivative with an Improved Safety Profile |
| Authors: | Benaím, Gustavo Hernandez-Rodriguez, Vanessa Mujica-Gonzalez, Sheira Parra-Gimenez, Nereida Plaza-Rojas, Lourdes Silva, May Li Garcia-Marchan, Yael paniz-mondolfi, Alberto Uzcanga, Graciela |
| Keywords: | Trypanosoma cruzi Amiodarone Dronedarona anti-Trypanosoma cruzi agent parental drug Drug Administration (FDA) |
| Issue Date: | 2012 |
| Publisher: | Antimicrobial agents and chemotherapy |
| Citation: | Vol. 56, Nº 7, p. 3720–3725 |
| Abstract: | Amiodarone, a commonly used antiarrhythmic, is also a potent and selective anti-Trypanosoma cruzi agent. Dronedarone is an amiodarone derivative in which the 2,5-diiodophenyl moiety of the parental drug has been replaced with an unsubstituted phe- nyl group aiming to eliminate the thyroid toxicity frequently observed with amiodarone treatment. Dronedarone has been ap- proved by the Food and Drug Administration (FDA), and its use as a safe antiarrhythmic has been extensively documented. We show here that dronedarone also has potent anti-T. cruzi activity, against both extracellular epimastigotes and intracellular amastigotes, the clinically relevant form of the parasite. The 50% inhibitory concentrations against both proliferative stages are lower than those previously reported for amiodarone. The mechanism of action of dronedarone resembles that of amiodarone, as it induces a large increase in the intracellular Ca21 concentration of the parasite, which results from the release of this ion from intracellular storage sites, including a direct effect of the drug on the mitochondrial electrochemical potential, and through alkalinization of the acidocalcisomes. Our results suggest a possible future repurposed use of dronedarone for the treatment of Chagas’ disease. |
| URI: | http://hdl.handle.net/10872/4389 |
| ISSN: | 0066-4804 |
| Appears in Collections: | Artículos Publicados |
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