Design, Synthesis and Biological Assessment of Ferulic Acid Derivatives as Inhibitors of β-Amyloid Oligomerization in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurological disorder that arises from the abnormal folding of β-amyloid (Aβ) and its subsequent aggregation. The resulting oligomers are hypothesized to be responsible for synaptic loss and neuronal cell death. Consequently, a potential therapeutic approach is to use a drug-like small molecule to bind Aβ and prevent its oligomerization, thus arresting the progression of AD. A class of small molecules that has been shown to interfere with the aberrant self-assembly of Aβ are phenolic acids. Among these, ferulic acid, a phenylalanine metabolite and potent antioxidant, was identified as an effective small molecule inhibitor of Aβ oligomerization. Herein, a library of ferulic acid derivatives was designed, synthesized and biologically evaluated for prevention or disruption of Aβ oligomerization.M.Sc.2019-01-11 00:00:0