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

A structure activity relationship study of curcumin analogues for the inhibition of amyloid β 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 β aggregation activity (leading to nanorod-like fragments), sufficient water solubility, and low cytotoxicity.

Design, synthesis and evaluation of curcumin-based fluorescent probes to detect Aβ fibrils.

Amyloid β fibrillation is an early event in Alzheimer's disease, so its detection is important to understand its roles in Alzheimer's disease. Curcumin, which has poor water solubility, has been reported to have many pharmacological activities including potent anti-amyloid β fibril activity in Alzheimer's disease. In this study, we found that curcumin analogues with the fluorescence property instead of non-inhibition of amyloid β fibrils.

Synthesis and evaluation of aminopyridine derivatives as potential BACE1 inhibitors.

To identify a new non-peptidyl BACE1 inhibitor, we focused on the aminopyridine structure, which binds to the active sites of BACE1. Synthesis of aminopyridine derivatives and evaluation of inhibitory activity against rBACE1 are described. The 2-aminopyridine moiety and/or 3-methoxybenzaldehyde could be converted to terminal acetylene derivatives by the Sonogashira method.