Design, Synthesis, and Biological Evaluation of (<i>E</i>)‑3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents

Novel (<i>E</i>)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides were designed and synthesized as new analogues of <b>1</b>, which showed interesting multifunctional neuroprotective effects, including antioxidative and antineuroinflammatory properties. Specifically, target compounds display excellent potency in scavenging reactive free radicals and demonstrate potent effects against various kinds of toxicities, including H₂O₂, 6-hydroxydopamine, and lipopolysaccharide in different types of neuronal cells. The antioxidative properties of the target compounds are more potent than that of <b>1</b>, and the antineuroinflammatory properties are less strong than that of <b>1</b>. According to the parallel artificial membrane permeation assay for the blood–brain barrier, target compounds possess greater blood–brain barrier (BBB) permeability than <b>1</b>. In short, due to improvement of the antioxidative effect, stability, and BBB permeability, (<i>E</i>)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides can thus be considered as potential multifunctional neuroprotective agents and serve as new lead candidates in the treatment of neurodegenerative diseases