Multicomponent, Fragment-Based, Synthesis of Polyphenol-containing Peptidomimetics and their Inhibiting Activity on Beta Amyloid Oligomerization

A new and concise fragment-based approach towards artificial (but "natural-based") complex polyphenols has been developed, exploiting the Ugi multicomponent reaction of phenol-containing simple substrates. The resulting library of compounds has been tested for the capacity to inhibit β-amyloid protein aggregation, as a possible strategy to develop new chemical entities to be used as a prevention or a therapy for Alzheimer's disease. Some of the members of the library have demonstrated, in Thioflavin assays, a highly promising activity in inhibiting aggregation for two β-amyloid peptides: Aβ1-42 and the truncated AβpE3-42.