Design, synthesis and biological evaluation of indane-2-arylhydrazinylmethylene-1,3-diones and indol-2-aryldiazenylmethylene-3-ones as a b-amyloid aggregation inhibitors.

ABSTRACT: Biological screening of (hetero)aromatic compounds allowed the identification of some novel inhibitors of Ab1–40 aggregation, bearing indane and indole rings as common scaffolds. Molecular decoration of lead compounds led to inhibitors exhibiting a potency, measured by the Thioflavin T fluorimetric assay, ranging from high to low micromolar IC50. The 2-(p-isopropylphenyldiazenylmethylene)indolone derivative 6c resulted as the most potent aggregation inhibitor exhibiting an IC50 of 1.4 mM, with complete lack of fibril formation as confirmed by transmission electron microscopy. Structure–activity relationships suggested that binding to the Ab peptide may be largely guided by p-stacking and hydrogen bond interactions.