Title:Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging
Volume: 16
Issue: 8
Author(s): Alexander Sturzu, Sumbla Sheikh*, Hubert Kalbacher, Thomas Nägele, Christopher Weidenmaier, Bettina M. Wegenast-Braun, Nadine Schilling, Ulrike Ernemann and Stefan Heckl
Affiliation:
- Department of Neuroradiology, University of Tubingen, Hoppe-Seyler-Str. 3, 72076 Tubingen,Germany
Keywords:
Curcumin, Alzheimer's disease, cytometry, amyloid plaques, confocal laser scanning microscopy, human prostate
cancer cell, antibiotics.
Abstract:
Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies
on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is
very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic
groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound
as an ester were performed and curcumin is mainly used as nutritional supplement.
Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic
substitution reaction. This is a small modification and should not impact the properties of curcumin
while introducing an easily accessible reactive amino group. This novel compound could be used to
couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the
aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent
dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and
flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic
mice depicting Alzheimer-like β-amyloid plaques.
Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific
uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized
for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not
strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM
experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β-
amyloid plaques.
Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be
coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.
