Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer’s Diseases
Copyright policy )Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer’s Diseases
A series of novel compounds 6a–h, 8i–1, 10s–v, and 16a–d were synthesized and evaluated, together with the known analogs 11a–f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 μM) and BChE (eqBChE IC50 = 0.28 μM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.
- Shandong Women’s University China (People's Republic of)
- Jiangsu Food and Pharmaceutical Science College China (People's Republic of)
- China Pharmaceutical University China (People's Republic of)
- Yantai University China (People's Republic of)
Cell Survival, Organic chemistry, PC12 Cells, Article, Structure-Activity Relationship, QD241-441, Alzheimer Disease, Catalytic Domain, Animals, Donepezil, structural modification, Binding Sites, structure-activity relationship, alzheimer’s disease, molecular docking, Rats, Molecular Docking Simulation, Kinetics, Neuroprotective Agents, Butyrylcholinesterase, Acetylcholinesterase, Tacrine, cytotoxicity, Cholinesterase Inhibitors, butyrylcholinesterase inhibitor, Alzheimer’s disease, acetylcholinesterase inhibitor
Cell Survival, Organic chemistry, PC12 Cells, Article, Structure-Activity Relationship, QD241-441, Alzheimer Disease, Catalytic Domain, Animals, Donepezil, structural modification, Binding Sites, structure-activity relationship, alzheimer’s disease, molecular docking, Rats, Molecular Docking Simulation, Kinetics, Neuroprotective Agents, Butyrylcholinesterase, Acetylcholinesterase, Tacrine, cytotoxicity, Cholinesterase Inhibitors, butyrylcholinesterase inhibitor, Alzheimer’s disease, acetylcholinesterase inhibitor
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