Propenylamide and propenylsulfonamide cephalosporins as a novel class of anti-MRSA β-lactams

Novel C(3) propenylamide and propenylsulfonamide cephalosporins have been synthesized and tested for their ability to inhibit the penicillin-binding protein 2′ (PBP2′) from Staphylococcus epidermidis and the growth of a panel of clinically relevant bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA). The most potent compounds inhibited the growth of MRSA strains with minimum inhibitory concentrations (MIC) as low as 1 μg/mL. The structure-activity relationship revealed the potential for further optimization of this new cephalosporin class.