title: Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis.
abstract: The currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine was effective against promastigotes in axenic cultures and showed an IC50 (concentration giving half-maximal inhibition) value of 8.4±0.7 µM. In addition, mefloquine, chloroquine and hydroxychloroquine were active against intracellular amastigotes in macrophage-infected cultures, presenting IC50 values of 1.56±0.19 µM, 0.78±0.08 µM and 0.67±0.12 µM, respectively. The ultrastructural analysis of chloroquine- or mefloquine-treated amastigotes showed an accumulation of multivesicular bodies in the cytoplasm of the parasite, suggesting endocytic pathway impairment, in addition to the formation of myelin-like figures and enlargement of the Golgi cisternae. CBA mice were infected with L. amazonensis in the ear dermis, and treated by oral and/or topical routes with chloroquine and mefloquine. Treatment of L. amazonensis-infected mice with chloroquine by the oral route reduced lesion size, which was associated with a decrease in the number of parasites in the ear, as well as the parasite burden in the draining lymph nodes. In contrast, mefloquine administration by both routes decreased the lesion size in infected mice without causing a reduction in parasite burden. Our results revealed a promising antileishmanial effect of chloroquine and suggest its use in cutaneous leishmaniasis treatment.
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Candeal, 40296-70, Salvador, Bahia, Brazil.
authors.forename: Vinícius Pinto Costa
authors.initials: VPC
authors.lastname: Rocha
authors.affiliation: Laboratório de Engenharia Tecidual e Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Candeal, 40296-70, Salvador, Bahia, Brazil.
authors.forename: Fabiana Regina
authors.initials: FR
authors.lastname: Nonato
authors.affiliation: Departamento de Ciências da Vida, Universidade do Estado da Bahia, Rua Silveira Martins, 2555, Cabula, 41150-000, Salvador, Bahia, Brazil.|Laboratório de Engenharia Tecidual e Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Candeal, 40296-70, Salvador, Bahia, Brazil.
authors.forename: Elisalva Teixeira
authors.initials: ET
authors.lastname: Guimarães
authors.affiliation: Faculdade de Medicina, Universidade Federal da Bahia, Avenida Reitor Miguel Calmon, s/n°, Vale do Canela, 40025-010, Salvador, Bahia, Brazil.|Laboratório de Patologia e Biointervenção, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Candeal, 40296-70, Salvador, Bahia, Brazil.
authors.forename: Luiz Antônio
authors.initials: LA
authors.lastname: Rodrigues de Freitas
authors.affiliation: Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Avenida São Rafael 2152, 41253-190, Salvador, Bahia, Brazil.|Laboratório de Engenharia Tecidual e Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Candeal, 40296-70, Salvador, Bahia, Brazil.
authors.forename: Milena Botelho Pereira
authors.initials: MBP
authors.lastname: Soares
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA
chemical_list: D000962:Antimalarials