Aminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis

Luciana Maria Ribeiro Antinarelli; Isabela de Oliveira Souza; Nicolas Glanzmann; Ayla das Chagas Almeida; Gabriane Nascimento Porcino; Eveline Gomes Vasconcelos; Adilson David da Silva; Elaine Soares Coimbra

doi:10.1016/j.exppara.2016.10.009

Aminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis

Exp Parasitol. 2016 Dec:171:10-16. doi: 10.1016/j.exppara.2016.10.009. Epub 2016 Oct 12.

Authors

Luciana Maria Ribeiro Antinarelli¹, Isabela de Oliveira Souza², Nicolas Glanzmann², Ayla das Chagas Almeida¹, Gabriane Nascimento Porcino³, Eveline Gomes Vasconcelos³, Adilson David da Silva², Elaine Soares Coimbra⁴

Affiliations

¹ 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.
² Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
³ Departamento de Bioquímica, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil.
⁴ 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.

PMID: 27743972
DOI: 10.1016/j.exppara.2016.10.009

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 (IC₅₀ values of 52.5 and 21.1 μM, respectively) and compounds 2a and 2c were active against intracellular amastigotes (IC₅₀ of 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.

Keywords: 4-Aminoquinoline derivatives; Leishmania amazonensis; Mitochondrial dysfunction; Quinolinylhydrazone derivatives.

MeSH terms

Aminoquinolines / chemistry
Aminoquinolines / pharmacology*
Aminoquinolines / toxicity
Animals
Erythrocytes / drug effects*
Erythrocytes / parasitology
Humans
Hydrazones / chemistry
Hydrazones / pharmacology*
Hydrazones / toxicity
Inhibitory Concentration 50
Leishmania mexicana / drug effects*
Macrophages / drug effects*
Macrophages / parasitology
Membrane Potential, Mitochondrial / drug effects
Mice
Mitochondria / drug effects
Reactive Oxygen Species / metabolism

Substances

Aminoquinolines
Hydrazones
Reactive Oxygen Species