Nine novel quinoline-chalcone hybrids were synthesized via a base-catalysed Claisen-Schmidt condensation of 6-fluoroquinoline-2-carbaldehyde, 8-fluoroquinoline-2-carbaldehyde or 6,8-difluoroquinoline-2-carbaldehyde with 4'-Br, 4'-Cl and 4'-F substituted acetophenones. The 2-methylquinoline intermediates were prepared by the Doebner-Miller reaction and oxidized to their corresponding quinoline-2-carbaldehydes before being condensed with the acetophenones. The structures of the quinoline chalcones were characterized by 1D and 2D NMR spectroscopy and confirmed by HRMS. The synthesised hybrid molecules were evaluated for their antibacterial activity against six standard bacterial strains, namely the Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), and the Gram-negative Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium. The synthesized compounds showed better or comparable antibacterial activity to known drugs (ciprofloxacin and levofloxacin) in the same assay, the most active being the 6,8-difluoroquinoline derivative with a para bromo moiety on the acetophenone derived portion of the molecule, showing MBC values of 5.2 and 20.9 μM against S. aureus and MRSA respectively.

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