Recent Advances in the Chemistry of β-Lactam Compounds as Selected Active-site Serine β-Lactamase Inhibitors

Abstract

<p>The β-lactamases catalyze the hydrolysis of the β-lactam bond of a variety of β-lactam antibiotics destroying their antibacterial activity. During the last decades, there has been an inexorable spread of β-lactamase genes into species that previously were not known to possess them. One approach to combat the action of the β--lactamase is to inhibit the enzyme. However, inhibition of β- lactamase alone is not sufficient. The ability to penetrate the external membrane of Gram-negative bacteria, chemical stability, pharmacokinetics and other factors are also important in determining whether an inhibitor is suitable or not for therapeutic use.</p><p> This review takes recent examples of synthetic β-lactam compounds developed as active-site serine β-lactamase inhibitors, emphasizing information on their structures and their activity against Ambler classes A, C and D β-lactamases. In addition, examples based on rational design by computerized molecular modeling of crystal structure of the native enzyme and mechanism of the enzyme action are highlighted.</p>