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

Bioorg Med Chem. 2008 May 1;16(9):4810-22. doi: 10.1016/j.bmc.2008.03.052. Epub 2008 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / chemistry*
  • Aniline Compounds / chemistry
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Caffeic Acids
  • Drug Design
  • Glycine / chemistry*
  • Molecular Structure
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Phenyl Ethers / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Time Factors
  • Xylenes / chemistry

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzamides
  • Caffeic Acids
  • Peptide Fragments
  • Peptides
  • Phenyl Ethers
  • Xylenes
  • amyloid beta-protein (1-40)
  • 1,3-xylenediamine
  • phenylethyl 3-methylcaffeate
  • Glycine