title: Furazolidone is a selective in vitro candidate against Leishmania (L.) chagasi: an ultrastructural study.
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 IC(50) values ranging between 0.47 and 0.73 microg/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.
authors.affiliation: Laboratory of Applied Toxinology on Antiparasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz, Av Dr Arnaldo 355, 8 degrees andar, Cerqueira César, CEP 01246-000, São Paulo, Brazil.
authors.forename: Juliana Quero
authors.initials: JQ
authors.lastname: Reimão
authors.forename: Noemi Nosomi
authors.initials: NN
authors.lastname: Taniwaki
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: Tempone
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005664:Furazolidone / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure*; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D005664:Furazolidone