Synthesis and inhibitory activity of acetamidophosphonic acids against metallo--lactamases

Metallo-beta-lactamases (MLs) are the target enzymes of antibiotic resistance and the phosphonic drugs make great influence to the development of contemporary medicine. Eleven acetamidophosphonic compounds were prepared and evaluated as inhibitors of the MLs. Compounds 4, 5, 7, 9, and 10 exhibited specific inhibitory activity against the ML NDM-1 and CcrA with an IC50 value range of 17 to 354M. Analysis of the structure-activity relationship showed that both the acetamido linker and the position of the substituent on the phenyl ring played an important role in the inhibitory abilities of the inhibitors against M beta/Ls.