Design, synthesis, and inhibition of novel ferulic acid derivatives on free fatty acid induced cellular lipid accumulation

Abnormal accumulation of hepatocyte lipids is a hallmark feature of NAFLD. Ferulic acid (FA), an ingredient with antioxidant activity in Chinese herbs, can be used to treat NAFLD by activating AMPK phosphorylation. In this study, we synthesized ten acrylic acid derivatives <b>A1-A10</b>. The inhibition of lipid accumulation showed that most target compounds could inhibit lipid accumulation at 400 μM; compound <b>A3</b> showed a better inhibitory effect than other compounds. Molecular docking results proved that <b>A3</b> could bind to PPARγ, and multiple binding sites existed in both the ferulic acid cohort and the substituted benzene cohort.