title: Aminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis.
abstract: In this study, we have investigated the antileishmanial activity of ten 7-chloro-4-quinolinylhydrazone derivatives. Among the compounds tested, compounds 2a and 2j presented activity against promastigotes (IC50values of 52.5 and 21.1 μM, respectively) and compounds 2a and 2c were active against intracellular amastigotes (IC50of 8.1 and 15.6 μM, respectively) of Leishmania amazonensis. The majority of compounds did not show toxicity against murine macrophages. Compound 2a exhibited low cytotoxicity to human erythrocytes and induced an oxidative imbalance in promastigote forms, reflected by an increase in the formation of reactive oxygen species (ROS) and a reduction of mitochondrial membrane potential. No alteration in the plasma membrane integrity of parasites was observed. Taken together, these results suggest that compound 2a is a selective antileishmanial agent, and preliminary observations suggest that its effects appear to be mediated by mitochondrial dysfunction.
authors.affiliation: Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Luciana Maria Ribeiro
authors.initials: LM
authors.lastname: Antinarelli
authors.affiliation: Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Isabela de Oliveira
authors.initials: IO
authors.lastname: Souza
authors.affiliation: Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Glanzmann
authors.affiliation: Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Ayla das Chagas
authors.initials: AD
authors.lastname: Almeida
authors.affiliation: Departamento de Bioquímica, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Gabriane Nascimento
authors.initials: GN
authors.lastname: Porcino
authors.affiliation: Departamento de Bioquímica, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Eveline Gomes
authors.initials: EG
authors.lastname: Vasconcelos
authors.affiliation: Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
authors.forename: Adilson David
authors.initials: AD
authors.lastname: da Silva
authors.affiliation: Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil. Electronic address: elaine.coimbra@ufjf.edu.br.
authors.forename: Elaine Soares
authors.initials: ES
authors.lastname: Coimbra
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D006835:Hydrazones; D017382:Reactive Oxygen Species
keywords: 4-Aminoquinoline derivatives; Leishmania amazonensis; Mitochondrial dysfunction; Quinolinylhydrazone derivatives