Polycyclic compounds as carriers for neuroactive non- steroidal anti-inflammatory drugs

Abstract

Recent scientific findings have highlighted the beneficial roles of polycyclic cage compounds in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Further interest into the chemistry of these compounds is stimulated by their remarkable ability to improve the pharmacokinetics profile of known neuroprotective agents. As potent lipophilic scaffolds, they can be employed to target the brain delivery of desired compounds. Inflammation is a key mediator of neuronal cell's degeneration as activated microglia and other inflammatory mediators propagate oxidative damage and neuronal loss. Epidemiological and clinical evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) slow down the progression and onset of neurodegenerative diseases. The beneficial effects of NSAIDs in ND can be attributed to their ability to inhibit cyclooxygenase enzymes thereby halting the biosynthesis of prostaglandins (PG) which are powerful mediators of inflammation. NSAIDs also inhibit the expression of pro- inflammatory genes. Despite their potential neuroprotective activity, NSAIDs are poorly lipophilic due to the presence of polar carboxylic acid groups and will therefore ionise at physiological pH, deterring them from reaching the desired site of action in the central nervous system (CNS).