Abstract
While β-lactam antibiotics remain among the most commonly prescribed pharmaceutical products, their effectiveness is currently threatened by the development of bacterial resistance. One key resistance mechanism is the ability to destroy the antibiotic through utilization of one or more types of β-lactamase. An effective countermeasure is to employ a combination product, consisting of both a β-lactam antibiotic and a β- lactamase inhibitor. Unfortunately, currently available inhibitors narrowly target only class A β-lactamases. This review will detail our research, directed toward the development of a useful broad-spectrum β-lactamase inhibitor. In the process, we have discovered new inhibitors capable of simultaneously inactivating class A, C, and D β-lactamase, produced conjugate siderophore / β-lactamase inhibitors, and explored the SARs of tunable, cephalosporin-derived β-lactamase inactivators. Useful synthetic methodology will be described, which simplifies the large scale production of many known inhibitors and which allows the rapid preparation of libraries of prospective inhibitors.
Keywords: Cephalosporin, lactamase, siderophore, lactamase inhibitor
Current Medicinal Chemistry
Title: The Discovery and Development of Modified Penicillin- and Cephalosporin- Derived β-Lactamase Inhibitors
Volume: 11 Issue: 14
Author(s): John D. Buynak
Affiliation:
Keywords: Cephalosporin, lactamase, siderophore, lactamase inhibitor
Abstract: While β-lactam antibiotics remain among the most commonly prescribed pharmaceutical products, their effectiveness is currently threatened by the development of bacterial resistance. One key resistance mechanism is the ability to destroy the antibiotic through utilization of one or more types of β-lactamase. An effective countermeasure is to employ a combination product, consisting of both a β-lactam antibiotic and a β- lactamase inhibitor. Unfortunately, currently available inhibitors narrowly target only class A β-lactamases. This review will detail our research, directed toward the development of a useful broad-spectrum β-lactamase inhibitor. In the process, we have discovered new inhibitors capable of simultaneously inactivating class A, C, and D β-lactamase, produced conjugate siderophore / β-lactamase inhibitors, and explored the SARs of tunable, cephalosporin-derived β-lactamase inactivators. Useful synthetic methodology will be described, which simplifies the large scale production of many known inhibitors and which allows the rapid preparation of libraries of prospective inhibitors.
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Cite this article as:
Buynak D. John, The Discovery and Development of Modified Penicillin- and Cephalosporin- Derived β-Lactamase Inhibitors, Current Medicinal Chemistry 2004; 11 (14) . https://dx.doi.org/10.2174/0929867043364847
DOI https://dx.doi.org/10.2174/0929867043364847 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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