Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells

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. Methoxy-lated phenyl-based chalcones 2a-1 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 mu W. The tested compound 2f showed suppression of iNOS and COX-2 enzymes. Moreover, compound 2f decreases in the expression of NF-kappa B and phosphorylated I kappa B in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKK beta as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.

Automated summary

Newly synthesized chalcone derivatives exhibit anti-inflammatory activity, with compound 2f showing the best inhibition of nitric oxide concentration. By inhibiting iNOS and COX-2 enzymes, compound 2f reduces the expression of NF-kappa B and phosphorylated I kappa B in LPS-stimulated macrophages.