Chemistry of Small Molecule Inhibitors in Self-Assembly of Alzheimers Disease Related Amyloid-Beta Peptide

Abstract

The role of the chemical structure, namely the effect of substituents, of small molecule inhibitors in selfassembly of Alzheimers disease related amyloid-beta peptide is discussed. The literature analysis is concentrated on the past 10 years and analyzed the structure of Aβ inhibitors pointing out common features. A basis set of 321 compounds is reviewed and a chemical map of the inhibitors is provided highlighting the most common substituents that appear in these molecules. Based on the findings, aromatic/heteroaromatic groups were found to be present in an overwhelming majority of inhibitors (95%). Acidic substituents appeared the second most common substituent group (67%) suggesting the importance of these motifs as possible binding units. Several structure activity relationship studies that support this role are also discussed. Keywords: Alzheimer's disease, amyloid, amyloid-beta peptide, self-assembly, fibrillogenesis, small molecule inhibitors, structure-activity relationship