Design, synthesis, biological evaluation and docking study of 5-oxo-4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

• DOI: 10.1016/j.ejmech.2013.07.038
• Publication Date: 2013-08-11T02:46:50Z
• Authors: Mehdi Khoobi; Masoumeh Alipour; Amirhossein Sakht...; Hamid Nadri; Alireza Moradi; Mehdi Ghandi; Saeed Emami; Alireza Foroumadi; Abbas Shafiee
• Keywords: Models, Molecular; Binding Sites; Molecular Structure; Models, Biological; 01 natural sciences; 0104 chemical sciences; Enzyme Activation; Molecular Docking Simulation; Structure-Activity Relationship; Butyrylcholinesterase; Catalytic Domain; Drug Design; Acetylcholinesterase; Benzopyrans; Cholinesterase Inhibitors

A series of fused coumarins namely 5-oxo-4,5-dihydropyrano[3,2-c]chromenes linked to N-benzylpyridinium scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The 1-(4-fluorobenzyl)pyridinium derivative 6g showed the most potent anti-AChE activity (IC50 value=0.038 μM) and the highest AChE/BuChE selectivity (SI>48). The docking study permitted us to rationalize the observed structure-affinity relationships and to detect possible binding modes.