New Resveratrol Derivatives Exhibit Acetylcholinesterase Inhibitory Properties and Decrease Reactive Oxygen Species Production in the SH-SY5Y Human Neuroblastoma Cell Line

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder involving different etiopathogenic mechanisms. Traditionally, acetylcholinesterase (AChE) inhibitors constitute a pharmacotherapeutic strategy for AD treatment. Resveratrol is a natural polyphenol, with anti-inflammatory, neuroprotective, anticarcinogenic, and antioxidant properties. To increase its bioavailability and solubility, a series of resveratrol derivatives were obtained, through microwave-assisted synthesis. This study aimed to evaluate the AChE inhibitory properties and the protective role against oxidative stress damage of 5 resveratrol analogs (M1 to M5) in SH-SY5Y cells. The studied compounds were not cytotoxic in a wide range of concentrations as determined by measurement of the activity of the enzyme lactate dehydrogenase. Treatment of SH-SY5Y cells at the AChE´s IC50s concentration (obtained by in vitro enzyme assays) significantly decreased the AChE enzyme activity in live cells, assessed by Ellman's method. The studied compounds did not present cytoprotective activities against H₂O₂ or KCl-induced-Ca²⁺ overload insults. However, through the dichlorofluorescein assay, 3 compounds decreased the endogenous production of reactive oxygen species (ROS). These results demonstrate that, in addition to their action as biologically active AChE inhibitors, some resveratrol derivatives exhibit neuroprotective effects against endogenous ROS production. These findings indicate that the new resveratrol derivatives could be considered as interesting entities with potential therapeutic applications for AD treatment.