Abstract

This work describes the synthesis and biological properties of a series of 2- and 4- pyridinylimines and pyridinylhydrazones. All compounds were evaluated in vitro against two species of Leishmania. The antioxidant activity and the toxic effect against murine peritoneal macrophages of the compounds were also performed. The synthesized compounds showed significant antileishmanial and antioxidant activities. For the antileishmanial assay, compounds 1a, 1d and 2a were active against the Leishmania species, and compound 2a was the most effective on promastigotes (IC₅₀ value = 3.38 µM) and amastigotes (IC₅₀ value = 18.96 µM) of L. amazonensis. Only compound 2a exhibited toxicity against murine peritoneal macrophages (CC₅₀ of 54.35 µM). However, this compound was 2.8 times more destructive to the intracellular amastigotes than the host cell. Regarding the antioxidant activity, compounds 1a and 2a exhibited a strong antioxidant effect (IC₅₀ values of 8.79 µM and 19.82 µM), compound 1a being better than the L-ascorbic acid (9.48 µM), used as reference.

Keywords: Heteroaromatic imines, heterocyclic Schiff bases, pyridinylimines, pyridinylhydrazones, antileishmanial activity, antioxidant activity.

Graphical Abstract