Compounds against inflammation and oxidative insult as potential agents for neurodegenerative disorders

Amides of proline, a feature encountered in nootropics, via the carboxylic group of ibuprofen, indomethacin, ketoprofen and naproxen were prepared. Proline carboxylic group was amidated or esterified with potential antioxidant or neuroprotective compounds. Proline was replaced by 4-hydroxyproline, 2-pipecolic acid or omitted, for investigating the contribution of structure to activity. Anti-inflammatory activity was determined, and selected compounds were examined for anti-dyslipidemic action, protection against brain ischaemia/reperfusion and brain penetration. Graphical abstract Amides of proline and related structures with NSAIDs were synthesized. They were amidated or esterified with antioxidant or neuroprotective compounds. Activity against lipid peroxidation, inflammation and brain ischaemia was evaluated.