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