Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging.

Abstract

Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (Abeta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (Ki=0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for Abeta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [18F]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [18F]8 is metabolically stable in the brain. These results suggest that [18F]8 is a suitable radioligand for Abeta plaque imaging.

• Authors: Eun Kyoung Ryu, Yearn Seong Choe, Kyung-Han Lee, Yong Choi, Byung-Tae Kim
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 20 Pg. 6111-9 (Oct 05 2006) ISSN: 0022-2623 [Print] United States
• PMID: 17004725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(4-(3-fluoropropoxy)-3-methoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one
• Amyloid
• Amyloid beta-Peptides
• Fluorine Radioisotopes
• Ligands
• Radiopharmaceuticals
• Styrenes
• Guaiacol
• methyl-3-methoxy-4-hydroxystyryl ketone
• Curcumin

Topics

• Amyloid (metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Brain (diagnostic imaging, metabolism)
• Curcumin (analogs & derivatives, chemical synthesis, pharmacokinetics)
• Fluorine Radioisotopes
• Guaiacol (analogs & derivatives, chemical synthesis, chemistry, pharmacokinetics)
• Isotope Labeling
• Ligands
• Male
• Mice
• Mice, Inbred ICR
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Styrenes (chemical synthesis, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon