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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 IC 50  values in a range between 2 and 16  μ M 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.

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