Phthalimide-Derived N-Benzylpyridinium Halides Targeting Cholinesterases: Synthesis and Bioactivity of New Potential Anti-Alzheimer's Disease Agents
详细信息 查看全文
- 作者：Mina Saeedi ; Maedeh Golipoor ; Mohammad Mahdavi ; Alireza Moradi ; Hamid Nadri ; Saeed Emami ; Alireza Foroumadi and Abbas Shafiee
- 关键词：1 ; 3-Dioxoisoindoline ; Acetylcholinesterase ; Alzheimer's disease ; Phthalimide ; Pyridinium
- 刊名：Archiv der Pharmazie
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：349
- 期：4
- 页码：293-301
- 全文大小：1180K
- ISSN：1521-4184
文摘
In order to develop potent dual-binding cholinesterase inhibitors as potential drugs for the treatment of Alzheimer's disease, we designed and synthesized phthalimide-based acetylcholinesterase (AChE) inhibitors (7) containing a substituted N-benzylpyridinium residue. The in vitro anti-cholinesterase assay employing the target compounds against AChE and butyrylcholinesterase (BChE) revealed the 2-fluorobenzylpyridinium derivative 7d as the most potent compound against both enzymes, with IC50 values of 0.77 and 8.71 μM. The docking study of compound 7d into the active site of AChE showed the gorge-spanning binding mode, in which the compound spans the narrow hydrophobic gorge from the bottom to the rim.