Eight novel chalcone analogues were designed and synthesized with 2H-pyran-2-one as the basic structure for the first time,and then were evaluated for their anti-bacterial activities against 4 strains,including Staphylococcus aureus 252,Escherichia coli 25922,Staphylococcus epidermidis 12228,and methicillin-resistant Staphylococcus aureus.The results demonstrated that the series of compounds exhibited the moderate activity against S. aureus 252,especially compound 12h,which the inhibitory activity was relatively good among all compounds and could be the potential compound for future structure-activity relationship research as lead compound.