Structure-activity relationships of polyphenols inhibiting lipopolysaccharide-induced NF-κB activation

Abstract

Most plant-derived phenolic compounds are synthesized as secondary metabolites in plants due to their defense strategies. Previous studies have reported the inhibitory effect of chalchones, one of polyphenols, on nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-dependent transcriptional activities in various cancer cells. However, detailed relationship between the structure and biological activity on the inhibition of NF-κB in the microglia is less defined. In this study, twenty-two polyphenols including sixteen hydroxy/methoxy chalcones, four 2H-chromenes, and two N-phenylacetamides were synthesized. Lipopolysaccharide (LPS) is a constituent of the outer membrane of the Gramnegative bacteria, which is widely employed as a proinflammatory stimulus in many experimental settings. The effects of polyphenol compounds synthesized on the inhibition of LPS-induced NF-κB activity in BV2 microglial cells were investigated, and the structural conditions to show better inhibitory effects were evaluated. Western blot analysis was performed on compounds showing good inhibitory effects. © 2012 The Korean Society for Applied Biological Chemistry.