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 µM, 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 µM. The mammalian cytotoxicity using LLC-MK2 cells resulted in an IC(50) value of 62.67 µM. 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.
Assuntos
Bepridil/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Animais , Bepridil/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sistemas Computacionais , Cricetinae , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Leishmania/classificação , Leishmania/efeitos dos fármacos , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Macaca mulatta , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , RNA de Protozoário/isolamento & purificação , Trypanosoma cruzi/efeitos dos fármacosRESUMO
A new cyclohexenone (1) and a new caffeoyl ester derivative (2), together with the known compounds (-)-isolariciresinol 3-alpha-O-beta-D-glucopyranoside (3), (+)-1-hydroxypinoresinol 1-O-beta-D-glucopyranoside (4), isoacteoside (5), luteolin 4'-O-beta-D-glucopyranoside (6), and indole-3-carboxylic acid (7), were isolated from the leaves of Bauhinia tarapotensis. The structures of these new compounds were determined by spectroscopic data analysis. The antioxidant activities of 1-7 were determined by measuring their free radical scavenging effects, using the 1,1-diphenyl-2-dipicrylhydrazyl free radical (DPPH) and Trolox equivalent antioxidant activity (TEAC) methods, and the coupled oxidation of beta-carotene and linoleic acid. Compounds 3-5 showed good activities in the DPPH and TEAC tests, while compounds 1 and 2 were active in the coupled oxidation of beta-carotene and linoleic acid bioassay.