Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach

Journal of venomous animals and toxins

Andre G. Tempone^2¹  Erika G. Pinto^1² 

[1]Centre for Parasitology and Mycology, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 351, 8°, Andar. Cerqueira César, São Paulo, SP CEP 01246-902 Brazil Find articles by Andre G. Tempone^2

[2]Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK^1

关键词: Leishmania;    Visceral leishmaniasis;    Amiodarone;    In vitro;    In vivo;   

DOI  :  10.1186/s40409-018-0166-7

学科分类：药理学

来源: BioMed Central

【 摘 要 】

Background Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. ( L. ) infantum and its in vitro and in vivo activity. Results The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC₅₀ value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC₅₀ value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum -infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.

【 授权许可】

CC BY