New Acyl Hydrazone Derivatives: Synthesis, Conformational Analysis by NMR Spectroscopy, and Enzyme Inhibitory and Antioxidant Activities in Alzheimer Disease

While the underlying causes of neurodegenerative diseases are varied, neuroinflammation is a common feature in most cases. Targeting neuroinflammation through anti-inflammatory strategies has emerged as a promising approach to prevent neurodegeneration. In addition, monoamine oxidase (MAO) inhibition has been suggested as an effective target in neurodegeneration. In this context, both cyclooxygenase (COX) and monoamine oxidase (MAO) inhibition have gained attention for their potential neuroprotective effects. In this study, novel hydrazone derivatives bearing benzoxazolinone structure were designed and synthesized as potential multifunctional MAO/COX inhibitors with antioxidant properties. Due to their structural and conformational flexibility, hydrazone compounds can form tautomers and isomers. Consequently, signals corresponding to these isomers have been detected in the 1H-NMR spectra of the synthesized compounds, prompting detailed spectral analyses (NOESY) to determine their isomeric ratios. In vitro biological activity tests have shown that most of the compounds exhibited significant COX inhibition and good antioxidant activity. MAO-B inhibitor capacity of the compounds is better than that of MAO-A. The cytotoxicity of all compounds in the series was negligible. Among the series, compounds 3g exhibited notable dual COX/MAO-B inhibition while 3c displayed potent MAO-B inhibition accompanied by antioxidant activity, highlighting their potential for further investigation.