New 2-amino-pyridinyl-N-acylhydrazones: Synthesis and identification of their mechanism of anti-inflammatory action

Abstract

Aims: The main aim of this paper was the synthesis and the evaluation of the anti-inflammatory activity of LASSBio-1828 (an amino-pyridinyl-N-acylhydrazone) and its respective hydrochloride, based on a p38α MAPK inhibitor (LASSBio-1824) previously synthesized by our group.

Main methods: The compounds were tested regarding their cell viability effect and on acute models of inflammation such as formalin-induced licking test, cell migration and inflammatory mediators quantification.

Key findings: Treatment with the compounds inhibited p38α, reduced inflammatory pain, cell migration and inflammatory mediators that participate on the MAPK pathway such as TNF-α and IL-1β.

Significance: Taken together, these results suggest that the synthesis of the corresponding hydrochloride of LASSBio-1828 enhanced its potency as a p38 inhibitor, and also that this compound could be considered a good anti-inflammatory drug candidate after further studies.

Keywords: Amino-Pyridinyl-N-acylhydrazones; Inflammation; NF-κB; TNF-α.