Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Aβ40 aggregation in vitro

A series of N-terminus benzamides of glycine-based symmetric peptides, linked to m-xylylenediamine and 3,40-oxydianiline spacers, were prepared and tested as inhibitors of b-amyloid peptide Ab1–40 aggregation in vitro. Compounds with good anti-aggregating activity were detected. Polyphenolic amides showed the highest anti-aggregating activity, with IC50 values in the micromolar range. Structure–activity relationships suggested that p–p stacking and hydrogen-bonding interactions play a key role in the inhibition of Ab1–40 self-assembly leading to amyloid fibrils.