Table of Contents Author Guidelines Submit a Manuscript
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 1523691, 9 pages
http://dx.doi.org/10.1155/2016/1523691
Research Article

Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism of Leishmania (L.) infantum

1Centre for Parasitology and Mycology, Institute Adolfo Lutz, Secretary of Health of São Paulo State, Avenida Dr. Arnaldo 351, 01246-000 São Paulo, SP, Brazil
2Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí, Rua Francisco Telles 250, 13202-550 Jundiai, SP, Brazil

Received 28 October 2015; Accepted 24 December 2015

Academic Editor: Juntra Karbwang

Copyright © 2016 Juliana Quero Reimão et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether the in vitro anti-Leishmania infantum and anti-Trypanosoma cruzi activities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50 values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treated Leishmania, but without plasma membrane disruption. Finally, in vitro combinations of amphotericin B, miltefosine, and pentamidine against L. infantum showed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for future in vivo efficacy studies against Leishmaniasis and Chagas’ disease.