Resistance to β-Lactam Antibiotics: Structure and Mechanism Based Design of β-Lactamase Inhibitors
Authors: Sandanayaka, V.P.; Prashad, A.S.
Source: Current Medicinal Chemistry, Volume 9, Number 12, June 2002 , pp. 1145-1165(21)
Publisher: Bentham Science Publishers
Abstract:Resistance to antibiotics is currently a major health concern in treating infectious diseases. The most common mechanism of resistance to β-lactam antibiotics is the production of β-lactamases, which destroy β-lactam antibiotics before they reach the bacterial target. Combination therapy, which involves treatment with a β-lactam antibiotic and a β-lactamase inhibitor, has been successfully used to control resistance during last two decades. Due to the lack of effectiveness of the currently available β-lactamase inhibitors against class C enzymes and new variants of β-lactamases, there is a need to develop an inhibitor with broad-spectrum activity. Since the discovery of clavulanic acid, there has been an enormous research effort in this area to identify better antibiotic / inhibitor combinations and to understand the molecular bases for interactions between β-lactam antibiotics, β-lactamases, and β-lactamase inhibitors. This review describes some of the structure- and mechanism-based approaches to design of new β-lactamase inhibitors and the study of probable mechanisms of inhibition using X-ray, electrospray ionization mass spectrometry, and molecular modeling techniques.
Document Type: Review Article
Publication date: June 2002
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.