Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based chalcones 2a-l and coumarin-based chalcones 3a-f were synthesized and compared for their inhibition of COX-2 enzyme and nitric oxide production suppression. Methoxylated phenyl-based chalcones showed better inhibition to COX-2 enzyme and nitric oxide suppression than the coumarin-based chalcones. Among the 18 synthesized chalcone derivatives, compound 2f exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC50 = 11.2 μM). The tested compound 2f showed suppression of iNOS and COX-2 enzymes. Moreover, compound 2f decreases in the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKKβ as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.
Keywords: Anti-inflammatory; Chalcones; LPS-induced RAW264.7 macrophages; Molecular docking; Nitric oxide inhibition; Nuclear factor kappa B.
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