Abstract
Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 ± 0.01 μM) is similar to the positive drug donepezil (0.059 ± 0.003 μM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease.
Keywords:
3-Arylbenzofuranone derivatives; Alzheimer’s disease; antioxidant activity; cholinesterase inhibitors; monoamine oxidase inhibitors.
MeSH terms
-
Acetylcholinesterase / metabolism
-
Alzheimer Disease / drug therapy*
-
Alzheimer Disease / metabolism
-
Animals
-
Anti-Anxiety Agents / chemical synthesis
-
Anti-Anxiety Agents / chemistry
-
Anti-Anxiety Agents / pharmacology*
-
Antioxidants / chemical synthesis
-
Antioxidants / chemistry
-
Antioxidants / pharmacology*
-
Benzofurans / chemical synthesis
-
Benzofurans / chemistry
-
Benzofurans / pharmacology*
-
Biphenyl Compounds / antagonists & inhibitors
-
Cholinesterase Inhibitors / chemical synthesis
-
Cholinesterase Inhibitors / chemistry
-
Cholinesterase Inhibitors / pharmacology*
-
Dose-Response Relationship, Drug
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Monoamine Oxidase / metabolism
-
Monoamine Oxidase Inhibitors / chemical synthesis
-
Monoamine Oxidase Inhibitors / chemistry
-
Monoamine Oxidase Inhibitors / pharmacology*
-
Picrates / antagonists & inhibitors
-
Rats
-
Rats, Wistar
-
Structure-Activity Relationship
Substances
-
Anti-Anxiety Agents
-
Antioxidants
-
Benzofurans
-
Biphenyl Compounds
-
Cholinesterase Inhibitors
-
Monoamine Oxidase Inhibitors
-
Picrates
-
1,1-diphenyl-2-picrylhydrazyl
-
Monoamine Oxidase
-
Acetylcholinesterase
Grants and funding
The authors are grateful to support from the Science and Shandong Provincial Natural Science Foundation [ZR2018LH021], the Innovation Project of Shandong Academy of Medical Sciences and Academic promotion programme of Shandong First Medical University [No. 2019LJ003].