Synthesis and evaluation of paeonol derivatives as potential multifunctional agents for the treatment of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Aβ) aggregation, oxidative stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a-5d merging three different functions, i.e., antioxidant, anti-acetylcholinesterase (AChE) activity, metal chelating agents for AD treatment have been synthesized and characterized. Biological assays revealed that compared with paeonol (309.7 μM), 5a-5d had a lower DPPH IC50 value (142.8-191.6 μM). 5a-5d could significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay in the concentration range of 5-40 μM. AChE activity was effectively inhibited by 5a-5d, with IC50 values in the range of 0.61-7.04 μM. 5a-5d also exhibited good metal-chelating ability. All the above results suggested that paeonol derivatives may be promising multifunctional agents for AD treatment.

• Authors: An Zhou, Hongfei Wu, Jian Pan, Xuncui Wang, Jiaming Li, Zeyu Wu, Ailing Hui
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 1 Pg. 1304-18 (Jan 14 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25594344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Cholinesterase Inhibitors
• paeonol

Topics

• Acetophenones (chemical synthesis, pharmacology, therapeutic use)
• Alzheimer Disease (drug therapy)
• Animals
• Cholinesterase Inhibitors (pharmacology)
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Docking Simulation
• Oxidative Stress (drug effects)
• PC12 Cells
• Rats
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Infrared
• Spectrophotometry, Ultraviolet