Full length articleAminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis

- A series of quinoline derivatives was synthesized and showed leishmanicidal effect.
- Compound 2a presented activity against promastigotes and amastigotes L. amazonensis.
- Compound 2a induces formation of ROS and a reduction of mitochondrial membrane potential.
- Compound 2a exhibited a selective and effective leishmanicidal effect.

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.