In vitro and in vivo synergistic interaction of substituted chalcone derivatives with norfloxacin against methicillin resistant Staphylococcus aureus

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-(40benzyloxyphenyl)-2-propen-1-one (2), 1-(400-biphenyl)-3-(3040-dihydroxyphenyl)-2-propen-1-one (11), 1(400-hydroxy-300-methylphenyl)3-(40-hydroxyphenyl)-2-propen-1-one (14), 3-(40-chlorophenyl)-1-(400hydroxyphenyl)2-propen-1-one (17), and LTG-oxime (27) showed significant antibacterial activity with MIC 12.5–50 mg mL 1 respectively. In combination studies, derivatives 2 and 14 significantly reduced the MIC of norfloxacin by up to 16 fold (FICI < 0.5), while derivatives 11, 17 and 27 reduced it by up to eight fold (FICI # 0.5). Flow cytometry analysis results clearly indicated that derivatives 2 and 14 significantly promote the accumulation and inhibition of the Et-Br efflux, which was further validated through spectrofluorimeter using clinical isolate MRSA-ST2071. In systemically infected Swiss albino mice model, both the compounds significantly (P < 0.001, P < 0.01) lowered the systemic bacterial load in blood, liver, kidney, lung and spleen tissues. This study supports the promising use of chalcones in the development of economical antibacterial combinations.