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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Reimao, Juliana Quero [1, 2] ; Mesquita, Juliana Tonini [1] ; Ferreira, Daiane Dias [1] ; Tempone, Andre Gustavo [1]
Total Authors: 4
[1] Secretary Hlth Sao Paulo State, Inst Adolfo Lutz, Ctr Parasitol & Mycol, Ave Dr Arnaldo 351, BR-01246000 Sao Paulo, SP - Brazil
[2] Fac Med Jundiai, Dept Morfol & Patol Basica, Rua Francisco Telles 250, BR-13202550 Jundiai, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Evidence-based Complementary and Alternative Medicine; 2016.
Web of Science Citations: 1

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: 08/11434-3 - Therapeutic combinations in visceral leishmaniasis: the antileishmanial potential of calcium channel blockers
Grantee:Juliana Quero Reimão Dalla Zanna
Support type: Scholarships in Brazil - Doctorate
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 type: Regular Research Grants
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 type: Scholarships in Brazil - Post-Doctorate