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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Evidence-based Complementary and Alternative Medicine; v. 2016, p. 9-pg., 2016-01-01.

Resumo

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)

• Processo FAPESP: 11/21970-2 - Moduladores seletivos de receptores de estrógeno como candidatos a fármacos para leishmaniose visceral: avaliação de associações de fármacos e investigação de mecanismos de ação leishmanicida
• Beneficiário: Juliana Quero Reimão Dalla Zanna
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/18756-1 - Avaliação de novas alternativas terapêuticas com fármacos sintéticos em modelos in vitro e experimentais de Leishmania (L.) infantum chagasi
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/11434-3 - Combinações terapêuticas na Leishmaniose Visceral: o potencial anti-leishmania de bloqueadores de canais de cálcio
• Beneficiário: Juliana Quero Reimão Dalla Zanna
• Modalidade de apoio: Bolsas no Brasil - Doutorado