The Role of Catechol in Caffeic Acid Phenethyl Ester Derivatives for Neuroprotective Effects

Neurodegenerative disorders are chronic, progressive neurological diseases characterized by damage to neuron cells. Oxidative stress and neuroinflammation play crucial roles in inducing these disorders. Caffeic acid phenethyl ester (CAPE) and its sulfone derivatives have demonstrated antioxidant and anti‐inflammatory effects, suggesting their potential as neuroprotective agents. In this study, 8 sulfone derivatives were designed and synthesized to explore the importance of catechol and structure–activity relationship of CAPE sulfone derivatives. Hydroxyl groups in catechol were replaced by ‐NO 2 , ‐NH 2 or ‐H, and their free radical scavenging, antioxidant, and anti‐inflammatory abilities were evaluated. It was found that the antioxidant activitiy was dominated by the catechol moiety in CAPE derivatives, while the anti‐inflammtory activity was not. Furthermore, the stabilization of catechol after affording H⋅ to eliminate free radicals possibly occurred through hydrogen bond ranther than electron transfer via p‐π conjugation. After the analysis, all the target compounds lost antioxidant properties at cellular level, and among them, the target compound ( E )‐2‐amino‐4‐(2‐(phenethylsulfonyl)vinyl) phenol with p ‐NH 2 and m ‐OH showed the best free radical scavaging acivitity and retained anti‐inflammatory activity.