Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer’s disease agents

• Main Authors: Yinling Yun, Yuhang Miao, Xiaoya Sun, Jie Sun, Xiaojing Wang
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: 2-arylbenzofuran derivatives; alzheimer's disease; cholinesterase inhibitors; β-secretase inhibitory activity
• Online Access: http://dx.doi.org/10.1080/14756366.2021.1940993
• ISSN: 1475-6366; 1475-6374

Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and β-secretase inhibitory activity. The IC50 value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L−1) is similar to donepezil (0.085 ± 0.01 µmol·L−1) and is better than baicalein (0.404 ± 0.04 µmol·L−1). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L−1). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.