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1. Synthesis and Evaluation of Paeonol Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer’s Disease

Author

An Zhou, Hongfei Wu, Jian Pan, Xuncui Wang, Jiaming Li, Zeyu Wu, and Ailing Hui

Subjects
Alzheimer’s disease, multifunctional agents, paeonol, acetylcholinesterase inhibitors, metal-chelating, biometal chelators, Organic chemistry, QD241-441
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.

Published
2015
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2. Synthesis and Evaluation of Paeonol Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer’s Disease

Author

Jiaming Li, Hongfei Wu, An Zhou, Zeyu Wu, Jian Pan, Ailing Hui, and Xun-Cui Wang

Subjects
Spectrometry, Mass, Electrospray Ionization, Antioxidant, Magnetic Resonance Spectroscopy, Spectrophotometry, Infrared, medicine.medical_treatment, Pharmaceutical Science, Pharmacology, medicine.disease_cause, PC12 Cells, Article, Analytical Chemistry, lcsh:QD241-441, chemistry.chemical_compound, lcsh:Organic chemistry, Alzheimer Disease, Drug Discovery, multifunctional agents, medicine, Animals, Humans, MTT assay, Physical and Theoretical Chemistry, metal-chelating, biometal chelators, IC50, Cholinesterase, biology, Organic Chemistry, Acetophenones, medicine.disease, Rats, Molecular Docking Simulation, Oxidative Stress, paeonol, Biochemistry, chemistry, Chemistry (miscellaneous), acetylcholinesterase inhibitors, biology.protein, Molecular Medicine, Spectrophotometry, Ultraviolet, Cholinesterase Inhibitors, Alzheimer's disease, Paeonol, Alzheimer’s disease, Oxidative stress, Acetylcholine, medicine.drug
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.

Published
2015

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