The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam
The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam
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DOI：
10.4155/fmc-2016-0078
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发表时间：
2016-06-01
影响因子：
4.2
通讯作者：
Schofield, Christopher J.
中科院分区：
文献类型：
--
作者：
Wang, David Yuxin;Abboud, Martine I.;Schofield, Christopher J.
Avibactam 是第一个投入临床使用的非 β-内酰胺 β-内酰胺酶抑制剂，是一种广谱丝氨酸 β-内酰胺酶抑制剂，具有对抗 A 类、C 类和某些 D 类 β-内酰胺酶的活性。我们概述了青霉素发现后不久的时期，开发临床上有用的非 β-内酰胺化合物作为抗菌剂，以及随后的青霉素结合蛋白和 β-内酰胺酶抑制剂。与β-内酰胺抑制剂一样，阿维巴坦通过涉及催化重要亲核丝氨酸残基的共价修饰的机制发挥作用。然而，与β-内酰胺抑制剂不同，阿维巴坦与其β-内酰胺酶靶标发生可逆反应。我们讨论了可能解释β-内酰胺和相关化合物作为抗菌剂和β-内酰胺酶抑制剂的明显特殊性质的化学因素，包括耐药性。讨论了未来的研究途径，包括作用与 β-内酰胺类似的非 β-内酰胺抗菌剂。
Avibactam, which is the first non-beta-lactam beta-lactamase inhibitor to be introduced for clinical use, is a broad-spectrum serine beta-lactamase inhibitor with activity against class A, class C, and, some, class D beta-lactamases. We provide an overview of efforts, which extend to the period soon after the discovery of the penicillins, to develop clinically useful non-beta-lactam compounds as antibacterials, and, subsequently, penicillin-binding protein and beta-lactamase inhibitors. Like the beta-lactam inhibitors, avibactam works via a mechanism involving covalent modification of a catalytically important nucleophilic serine residue. However, unlike the beta-lactam inhibitors, avibactam reacts reversibly with its beta-lactamase targets. We discuss chemical factors that may account for the apparently special nature of beta-lactams and related compounds as antibacterials and beta-lactamase inhibitors, including with respect to resistance. Avenues for future research including non-beta-lactam antibacterials acting similarly to beta-lactams are discussed.