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

Author(s)

Reimao, Juliana Quero ; Mesquita, Juliana Tonini ; Ferreira, Daiane Dias ; Tempone, Andre Gustavo

• Document type: Journal article
• Source: Evidence-based Complementary and Alternative Medicine; v. 2016, p. 9-pg., 2016-01-01.

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 mu 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. (AU)

• FAPESP's process: 11/21970-2 - SELECTIVE ESTROGEN RECEPTOR MODULATORS AS DRUG CANDIDATES FOR VISCERAL LEISHMANIASIS: EVALUATION OF DRUG COMBINATIONS AND INVESTIGATION OF LEISHMANICIDAL MECHANISMS OF ACTION
• Grantee: Juliana Quero Reimão Dalla Zanna
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/18756-1 - Evaluation of novel alternative therapies with synthetic drugs using in vitro and experimental models of Leishmania (L.) infantum chagasi
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/11434-3 - Therapeutic combinations in Visceral Leishmaniasis: the antileishmanial potential of calcium channel blockers
• Grantee: Juliana Quero Reimão Dalla Zanna
• Support Opportunities: Scholarships in Brazil - Doctorate