Furazolidone is a selective in vitro candidate against Leishmania (L.) chagasi: an ultrastructural study |
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Authors: | Juliana Quero Reimão Noemi Nosomi Taniwaki André Gustavo Tempone |
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Institution: | 1. Laboratory of Applied Toxinology on Antiparasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 355, 8° andar, Cerqueira César, CEP 01246-000, S?o Paulo, S?o Paulo, Brazil
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Abstract: | The current treatment for leishmaniasis is unsatisfactory due to toxic side effects, high cost, and problems with drug resistance.
Various approaches have been used to identify novel drug candidates to treat Leishmania sp. parasites including the use of re-purposed drugs. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial
activity and is used for the treatment of giardiasis. In the present work, we determined the in vitro antileishmanial activity
of furazolidone and its ability to induce ultrastructural alterations of parasites. Promastigotes of Leishmania (L.) chagasi, Leishmania (V.) braziliensis, Leishmania (L.) major, and Leishmania (L.) amazonensis were highly susceptible to furazolidone, with IC50 values ranging between 0.47 and 0.73 μg/mL. Furazolidone was also very effective against L. chagasi intracellular amastigotes, and despite mammalian cytotoxicity, the selectivity index was 8.0 in human monocytes. The drug
also had limited toxicity in mice erythrocytes. Furazolidone demonstrated specific activity against Leishmania, a potential consequence of the lack of macrophage nitric oxide activation. As determined by electron transmission microscopy,
drug treatment induced severe damage to the parasite mitochondria and nucleus. This older oral drug is an effective agent
for the treatment of L. (L.) chagasi in vitro and is a novel candidate for further experimental studies. |
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