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

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 15; pp. 4635 - 4638
• Main Authors: Pohlmann, Jens, Vasilevich, Natalya I, Glushkov, Andrei I, Kellenberger, Laurenz, Shapiro, Stuart, Caspers, Patrick, Page, Malcolm GP, Danel, Franck
• Format: Journal Article
• Language: English
• Published: 01-08-2010
• Subjects: Cephalosporins; Staphylococcus aureus
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.05.110

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 kg/mL. The structure-activity relationship revealed the potential for further optimization of this new cephalosporin class.