m-Terphenylamines, Acting as Selective COX-1 Inhibitors, Block Microglia Inflammatory Response and Exert Neuroprotective Activity

Inhibition of cyclooxygenase-2 (COX-2) has been extensively studied as an approach to reduce proinflammatory markers in acute brain diseases, but the anti-neuroinflammatory role cyclooxygenase-1 (COX-1) inhibition rather neglected. We report that m-terphenylamine derivatives are selective COX-1 inhibitors, able block microglia inflammatory response and elicit a neuroprotective effect. These compounds were synthesized via three-component reaction chalcones, β-ketoesters, primary amines, followed by hydrolysis/decarboxylation ester group. Together with their synthetic intermediates some urea derivatives, they inhibitors COX-2. The which also analyzed for ability oxidative response. Compound 3b presented interesting anti-inflammatory profile reducing nitrite release, ROS overproduction, cell death organotypic hippocampal cultures subjected LPS. thus show is promising provide enhanced neuroprotection against processes, crucial development plethora neurodegenerative injuries.