Title:Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease
Volume: 15
Issue: 13
Author(s): Syed Nasir Abbas Bukhari and Ibrahim Jantan
Affiliation:
Keywords:
Alzheimer’s disease, anti-amyloid effect, β-amyloid, brain, neuroprotective effect, synthetic curcumin analogs.
Abstract: There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the
currently available AD treatments provide only momentary and incomplete symptomatic relief.
Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated
for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The
ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three
structural characteristics such as the presence of two aromatic end groups and their co-planarity, the
length and rigidity of the linker region and the substitution conformation of these aromatics. However,
curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and
poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with
analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to
enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of
curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid
and discussed their potential as therapeutic and diagnostic agents for AD.
