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

<p>The &#946;-lactamases catalyze the hydrolysis of the &#946;-lactam bond of a variety of &#946;-lactam antibiotics destroying their antibacterial activity. During the last decades, there has been an inexorable spread of &#946;-lactamase genes into species that previously were not known to possess them. One approach to combat the action of the &#946;--lactamase is to inhibit the enzyme. However, inhibition of &#946;- 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 &#946;-lactam compounds developed as active-site serine &#946;-lactamase inhibitors, emphasizing information on their structures and their activity against Ambler classes A, C and D &#946;-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>