Synthesis, molecular docking study, and in vivo biological evaluation of pyrazolopyridines derived from monocarbonyl curcumin analogues as potential anti-inflammatory agents

Abstract

Background: Pyrazolopyridines are heterocyclic compounds with nitrogen atoms in the ring, and they have been used as one of the important pharmacophores in drug design. Pyrazole derivatives have been synthesised and applied in the pharmaceutical industry as active drugs. The recent commercial success of pyrazole COX-2 inhibitors has brought even more attention to the significance of this heterocyclic ring in medicinal chemistry. Objective: This study aimed to synthesise new compounds as anti-inflammatory candidates from the pyrazolopyridine group. Method: Synthesis was carried out using the Claisen-Schmidt reaction through condensation of substituted benzaldehyde and 4-piperidone to produce mono-ketone curcumin analogues, which were then cyclised with phenylhydrazine. The results of the synthesis were characterised using FT-IR, 1H-NMR, and MS. Docking analysis was performed on the 3LN1 protein with MOE 2021.0901. Furthermore, an in vivo anti-inflammatory test was applied using a plethysmometer. Results: The synthesis results obtained two pyrazolopyridine compounds, and the docking results showed that both of these synthesised compounds could interact with the COX-2 receptor binding site. Conclusion: Compound 2 demonstrated good anti-inflammatory activities. This strategy is in the preliminary stages of identifying novel substances that may be used as anti-inflammatory agents in the future.