Multicomponent Synthesis of Polyphenols and Their In Vitro Evaluation as Potential β-Amyloid Aggregation Inhibitors

• Main Authors: Denise Galante, Luca Banfi, Giulia Baruzzo, Andrea Basso, Cristina D’Arrigo, Dario Lunaccio, Lisa Moni, Renata Riva, Chiara Lambruschini
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Molecules
• Subjects: multicomponent reactions; polyphenols; β-amyloid proteins; Alzheimer’s disease; Ugi reaction; β-lactams
• Online Access: https://www.mdpi.com/1420-3049/24/14/2636
• ISSN: 1420-3049

While plant polyphenols possess a variety of biological properties, exploration of chemical diversity around them is still problematic. Here, an example of application of the Ugi multicomponent reaction to the combinatorial assembly of artificial, yet “natural-like”, polyphenols is presented. The synthesized compounds represent a second-generation library directed to the inhibition of β-amyloid protein aggregation. Chiral enantiopure compounds, and polyphenol-β-lactam hybrids have been prepared too. The biochemical assays have highlighted the importance of the key pharmacophores in these compounds. A lead for inhibition of aggregation of truncated protein AβpE3-42 was selected.