کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6291763 | 1302500 | 2011 | 5 صفحه PDF | دانلود رایگان |

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 (IC50) 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 IC50 values in the range of 3 to 7 μM. The mammalian cytotoxicity using LLC-MK2 cells resulted in an IC50 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.
Highlights⺠Bepridil showed in vitro activity against Leishmania and T. cruzi parasites. ⺠Bepridil failed to treat L. (L.) chagasi-infected hamsters. ⺠Real-time PCR was highly sensitive for the quantification of living amastigotes. ⺠The method allow a fast and accurate screening of lead candidates in hamster model.
Journal: Experimental Parasitology - Volume 128, Issue 2, June 2011, Pages 111-115