New adamantane-derived nitrones with potential antioxidant and neuroprotective activities

<p>In this project, 13 novel adamantane-based nitrones were synthesized using pharmacologically relevant scaffolds such as amantadine, memantine, rimantadine, and related adamantylamines. A new, efficient synthetic strategy was developed, enabling the introduction of diethoxyphosphoryl, diethoxyphosphorylmethyl, and ethoxycarbonyl groups under mild and sustainable conditions. The lipophilicity of the obtained compounds was determined by both computational and chromatographic methods, revealing significant variation depending on the nature of the substituents and starting materials.</p><p><br /></p><p>Antioxidant and neuroprotective properties were evaluated in collaboration with Professor Dimitra Hadjipavlou-Litina (Aristotle University of Thessaloniki, Greece) and Professor José Marco-Contelles (Institute of Organic Chemistry, CSIC, Madrid, Spain). Antioxidant activity was assessed via lipid peroxidation inhibition, lipoxygenase (LOX) assays, and radical scavenging (DPPH and ABTS). Neuroprotective potential was studied using SH-SY5Y neuroblastoma cells in in vitro models of oxidative (R/O) and phosphorylation-induced (OA) stress.</p>