Synthesis and biological evaluation of penam sulfones as inhibitors of β-lactamases

The chemical synthesis of a series of new penam sulfone derivatives bearing a 2β-substituted-oxyimino and -hydrazone substituents, their β-lactamase inhibitory properties against selected enzymes representing class A and C β-lactamases are reported. The oxime containing penam sulfones strongly inhibited the Escherichia coli TEM-1 and Klebsiella pneumoniae cefotaximase (CTX-1) enzymes, but moderately inhibited the Pseudomonas aeruginosa 46012 cephalosporinase; while the 2β-substituted-hydrazone derivatives were generally less active against these enzymes. Furthermore, most of the inhibitors enhanced the antibacterial activities of piperacillin (PIP) and ceftazidime (CAZ) particularly against TEM-1 and CTX-1 producing bacterial strains.

Synthesis of 2β-substituted-oxyimino and -hydrazone penam sulfones and their β-lactamase inhibitory activities against class A and C β-lactamases are presented.Figure optionsDownload as PowerPoint slide