In vitro and experimental therapeutic studies of the calcium channel blocker bepridil.: Detection of viable Leishmania (L.) chagasi by real-time PCR

Autor(es)

Reimao, Juliana Q. ^[1] ; Colombo, Fabio A. ^[2] ; Pereira-Chioccola, Vera L. ^[2] ; Tempone, Andre G. ^[1]

Afiliação do(s) autor(es)

^[1] Dept Parasitol, Lab Appl Toxinol Antiparasit Drugs, BR-01246902 Sao Paulo - Brazil

^[2] Dept Parasitol, Mol Biol Lab, BR-01246902 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Parasitology; v. 128, n. 2, p. 111-115, JUN 2011.
• Citações Web of Science: 24

Resumo

The need for novel and efficacious drugs against neglected parasitic diseases, such as Leishmaniasis and American Trypanosomiasis, is certainly apparent. In this work, we evaluated the in vitro potential of the calcium channel blocker bepridil against Leishmania spp. and Trypanosoma cruzi parasites and exploited an experimental assay using a hamster model with Leishmania (L.) chagasi, with a real-time PCR method for therapeutic evaluation. Bepridil was in vitro effective against promastigotes and intracellular amastigotes of L. (L.) chagasi, with 50% inhibitory concentration (IC(50)) values of 3.81 and 21.55 mu M, respectively. Leishmania (L.) amazonensis, L. (L.) major and L. (V.) braziliensis promastigotes and T. cruzi trypomastigotes were also susceptible to bepridil, with in vitro selectivity toward parasites and IC(50) values in the range of 3 to 7 mu M. The mammalian cytotoxicity using LLC-MK2 cells resulted in an IC(50) value of 62.67 mu M. However, bepridil showed lack of activity at 12 mg/kg in the experimental hamster model infected with L. (L.) chagasi parasites. However, the real-time PCR was a promising tool for the accurate and fast quantification of RNA of living parasites in the liver and spleen of infected hamsters after treatment, eliminating time-consuming light microscopy evaluations. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• 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
• Processo FAPESP: 08/00520-6 - Leishmaniose visceral americana no Estado de São Paulo: estudo de transmissores alternativos e da diversidade gênica entre os isolados
• Beneficiário: Vera Lúcia Pereira Chioccola
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/09260-7 - Combinações terapêuticas na leishmaniose visceral: o potencial anti-leishmania de bloqueadores de canais de cálcio e o uso de nanoformulações lipossomais
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/57245-7 - Leishmaniose visceral americana no estado de São Paulo: estudo de transmissores alternativos
• Beneficiário: Fabio Antonio Colombo
• Modalidade de apoio: Bolsas no Brasil - Doutorado