Antiproliferative effect of a benzofuran derivate based on the structure of amiodarone on Leishmania donovani affecting mitochondria, acidocalcisomes and intracellular Ca2+ homeostasis

Publication date: Available online 20 February 2019Source: Parasitology InternationalAuthor(s): Nathalia Martinez-Sotillo, Andrea Pinto-Martínez, Elżbieta Hejchman, Gustavo BenaimAbstractLeishmaniasis is a parasitic disease representing an important problem of public health. Visceral leishmaniasis, resulting from infection with Leishmania donovani, causes considerable mortality and morbidity in the poorest region of the word. At present there is no current effective treatment, since the approved, drugs are expensive and are not free of undesirable side effects. Therefore, there is a need for the identification of new drugs. In this context, the parasite Ca2+ regulatory mechanisms in which mitochondria and acidocalcisomes are involved have been postulated as important targets for several trypanocidal drugs. Thus, amiodarone and dronedarone, common human antiarrythmics, exert its known action on these parasites through the disruption of the intracellular Ca2+ homeostasis. AMIODER is a benzofuran derivate based on the structure of amiodarone that recently demonstrates a significant effect on Trypanosoma cruzi. We now report the effect of AMIODER on Leishmania donovani demonstrating that it inhibit the growth of promastigotes and also of amastigotes inside macrophages, the clinically relevant stage of the parasite, obtaining IC50 values significantly lower than those reported for T. cruzi. We also show that this compound disrupted Ca2+ homeostasis in L. donovani, through its ac...

Source: Parasitology International - February 20, 2019 Category: Parasitology Source Type: research