A series of benzofuran-based chalconoids 6aev were designed and synthesized as new potential AChE inhibitors. The in vitro assay of synthesized compounds 6aev showed that most compounds had significant anti-AChE activity at micromolar or sub-micromolar levels. Among the tested compounds, 3- pyridinium derivative 6m bearing N-(2-bromobenzyl) moiety and 7-methoxy substituent on the benzofuran ring exhibited superior activity. This compound with IC50 value of 0.027 mM was as potent as standard drug donepezil.