Synthesis and biological evaluation of novel β-lactam-metallo β-lactamase inhibitors.

β-lactamases are enzymes that deactivate β-lactam antibiotics through a hydrolysis mechanism. There are two known types of β-lactamases: serine β-lactamases (SBLs) and metallo β-lactamases (MBLs). The two existing strategies to overcome β-lactamase-mediated resistance are (a) to develop novel β-lactam antibiotics that are not susceptible to hydrolysis by these enzymes; or (b) to develop β-lactamase inhibitors that deactivate the enzyme and thereby restore the efficacy of the co-administered antibiotics.