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

Molecules

An Zhou¹  Hongfei Wu²  Jian Pan¹  Xuncui Wang²  Jiaming Li²  Zeyu Wu¹  Ailing Hui¹ 

[1] Institute of Natural Medicine, Hefei University of Technology, Hefei 230009, Anhui, China; E-Mails:;Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui, China; E-Mails:

关键词: Alzheimer’s disease;    multifunctional agents;    paeonol;    acetylcholinesterase inhibitors;    metal-chelating;    biometal chelators;   

DOI  :  10.3390/molecules20011304

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.