Pd-Catalyzed Direct Modification of an Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues.
Lin-Xi WanShi-Xing MiaoZhen-Xiang HeXiaohuan LiXian-Li ZhouFeng GaoPublished in: ACS omega (2021)
Palladium/BuAd2P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer's disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).
Keyphrases
- oxidative stress
- single cell
- induced apoptosis
- cognitive decline
- room temperature
- molecular docking
- drug induced
- diabetic rats
- cell cycle arrest
- molecular dynamics
- emergency department
- adverse drug
- cell therapy
- small molecule
- bone marrow
- stem cells
- structure activity relationship
- brain injury
- endoplasmic reticulum stress
- protein protein
- cerebral ischemia
- cell death