The total synthesis of berberine and selected analogues, and their evaluation as amyloid beta aggregation inhibitors.

The total synthesis of berberine and selected analogues. And their evaluation as amyloid ß (Aß) aggregation inhibitors is described. The key step in the synthesis, the assembly of the berberine framework, was accomplished using an intermolecular Heck reaction. Berberine analog 17 incorporating a tertiary amine moiety showed good anti Aß aggregation activity, water solubility, and almost no toxicity to nerve cells.

Design, synthesis and evaluation of diaryl γ-dihydropyrone derivatives as cyclocurcumin mimetics and inhibitors of the aggregation of amyloid ß.

A structure activity relationship study of cyclocurcumin-derived, diaryl γ-dihydropyrone-based inhibitors of amyloid ß aggregation is described. Optimization of the diaryl γ-dihydropyrone framework and two phenolic rings resulted in the identification of diaryl γ-dihydropyrone type cyclocurcumin analogue AY1511, which exhibited potent anti-amyloid ß aggregation activity (leading to nanorod-like fragments), sufficient water solubility, and low cytotoxicity.

Design, synthesis, and evaluation of a water soluble C5-monoketone type curcumin analogue as a potent amyloid ß aggregation inhibitor.

A structure activity relationship study of curcumin analogues for the inhibition of amyloid ß aggregation is described. Optimization of the o-phenol and olefin spacer resulted in the identification of the C5-monoketone type curcumin analogue AY1319, which exhibited potent anti-amyloid ß aggregation activity (leading to nanorod-like fragments), sufficient water solubility, and low cytotoxicity.