Recent advances in the chemistry of beta-lactam compounds as selected active-site serine beta-lactamase inhibitors

The beta-lactamases catalyze the hydrolysis of the beta-lactam bond of a va riety of beta-lactam antibiotics destroying their antibacterial activity. D uring the last decades, there has been an inexorable spread of beta-lactama se genes into species that previously were not known to possess them. One approach to combat the action of the beta-lactamase is to inhibit the e nzyme. However, inhibition of beta-lactamase alone is not sufficient. The a bility to penetrate the external membrane of Cram-negative bacteria, chemic al stability, pharmacokinetics and other factors are also important in dete rmining whether an inhibitor is suitable or not for therapeutic use. This review takes recent examples of synthetic beta-lactam compounds develo ped as active-site serine beta-lactamase inhibitors, emphasizing informatio n on their structures and their activity against Ambler classes A, C and D beta-lactamases. In addition, examples based on rational design by computer ized molecular modeling of crystal structure of the native enzyme and mecha nism of the enzyme action are highlighted.