Antileishmanial activity and ultrastructural alterations of Leishmania (L.) chagasi treated with the calcium channel blocker nimodipine |
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Authors: | André Gustavo Tempone Noemi Nosomi Taniwaki and Juliana Quero Reim?o |
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Institution: | (1) Laboratório de Toxinologia Aplicada, Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 355, 8° andar, CEP 01246-000 S?o Paulo, S?o Paulo, Brazil |
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Abstract: | In a search for novel antileishmanial drugs, we investigated the activity of the calcium channel blocker nimodipine against
Leishmania spp. and explored the ultrastructural damages of parasites induced by nimodipine after a short period of incubation. Nimodipine
was highly effective against promastigotes and intracellular amastigotes of Leishmania (L.) chagasi, with 50% inhibitory concentration values of 81.2 and 21.5 μM, respectively. Nimodipine was about fourfold more effective
than the standard pentavalent antimony against amastigotes and showed a Selectivity Index of 4.4 considering its mammalian
cells toxicity. Leishmania (L.) amazonensis and Leishmania (L.) major promastigotes were also susceptible to nimodipine in a range concentration between 31 and 128 μM. Ultrastructural studies
of L. (L.) chagasi revealed intense mitochondria damage and plasma membrane blebbing, resulting in a leishmanicidal effect as demonstrated by
the lack of mitochondrial oxidative metabolism. The amastigote-killing effect suggests other mechanism than macrophage activation,
as no upregulation of nitric oxide was seen. This calcium channel blocker is an effective in vitro antileishmanial compound
and if adequately studied could be used as a novel drug candidate or as a novel drug lead compound for drug design studies
against leishmaniasis. |
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