Design and Synthesis of Ferulic Acid Derivatives with Enhanced Antioxidant and Neuroprotective Activities: Discovery of Dual Antioxidant Agent

Ferulic acid (FA) is well known for its antioxidant properties and neuroprotective effects. To enhance these biological activities, we designed a novel series of FA derivatives by introducing a phenyl group at the α-position of the carboxyl moiety. Further structural modifications were achieved by incorporating hydroxy or alkoxy substituents at various positions on the two aromatic rings. A series of these derivatives were synthesized and evaluated for their antioxidant capacity using the DPPH radical scavenging assay, as well as their cytoprotective effects against oxidative stress in Neuro-2a cells. Among the synthesized compounds, one derivative exhibited significantly enhanced activity in both assays. Mechanistic studies indicated that this heightened efficacy is attributable to a unique reaction pathway involving dual antioxidant mechanisms.