Thirty chalcone derivatives were synthesized via a base catalyzed Claisen Schmidt condensation and evaluated for their anti-methicillin-resistant Staphylococcus aureus (MRSA) activity alone and in combination with norfloxacin. Among these, 5 derivatives namely trans-3-(1H-indol-3-yl)-1-(4′-benzyloxyphenyl)-2-propen-1-one (2), 1-(4″-biphenyl)-3-(3′4′-dihydroxyphenyl)-2-propen-1-one (11), 1-(4″-hydroxy-3