In Vitro Anti-Trypanosoma cruzi Activity of Dronedarone, a Novel Amiodarone Derivative with an Improved Safety Profile
Registro en:
Vol. 56, Nº 7, p. 3720–3725
0066-4804
doi:10.1128/AAC.00207-12
Autor
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
Institución
Resumen
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.