Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives

• Scopoletin derivatives with pyridinium moiety were synthesized as AChE inhibitors.
• 2-Fluorobenzylpyridinium derivative showed the strongest activity (IC50 = 0.215 μM).
• Docking studies showed that scopoletin portion was bound to the PAS of the AChE.
• From docking results, N-benzylpyridinium residue was bound to the CAS of enzyme.
• The compounds in the synthesized series were selective against AChE over BuChE.

A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellman’s method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215 ± 0.015 μM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site.

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