Bioorganic & Medicinal Chemistry 2008-05-01

Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Abeta1-40 aggregation in vitro.

Saverio Cellamare, Angela Stefanachi, Diana A Stolfa, Teodora Basile, Marco Catto, Francesco Campagna, Eddy Sotelo, Pasquale Acquafredda, Angelo Carotti

Index: Bioorg. Med. Chem. 16(9) , 4810-22, (2008)

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Abstract

A series of N-terminus benzamides of glycine-based symmetric peptides, linked to m-xylylenediamine and 3,4'-oxydianiline spacers, were prepared and tested as inhibitors of beta-amyloid peptide Abeta(1-40) aggregation in vitro. Compounds with good anti-aggregating activity were detected. Polyphenolic amides showed the highest anti-aggregating activity, with IC(50) values in the micromolar range. Structure-activity relationships suggested that pi-pi stacking and hydrogen-bonding interactions play a key role in the inhibition of Abeta(1-40) self-assembly leading to amyloid fibrils.