McGeary Ross P, Tan Daniel Tc, Schenk Gerhard
School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Future Med Chem. 2017 May;9(7):673-691. doi: 10.4155/fmc-2017-0007. Epub 2017 May 15.
The global overuse of antibiotics has led to the emergence of drug-resistant pathogenic bacteria. Bacteria can combat β-lactams by expressing β-lactamases. Inhibitors of one class of β-lactamase, the serine-β-lactamases, are used clinically to prevent degradation of β-lactam antibiotics. However, a second class of β-lactamase, the metallo-β-lactamases (MBLs), function by a different mechanism to serine-β-lactamases and no inhibitors of MBLs have progressed to be used in the clinic. Bacteria that express MBLs are an increasingly important threat to human health. This review outlines various approaches taken to discover MBL inhibitors, with an emphasis on the different chemical classes of inhibitors. Recent progress, particularly new screening methods and the rational design of potent MBL inhibitors are discussed.
全球抗生素的过度使用已导致耐药病原菌的出现。细菌可通过表达β-内酰胺酶来对抗β-内酰胺类药物。一类β-内酰胺酶即丝氨酸-β-内酰胺酶的抑制剂在临床上用于防止β-内酰胺类抗生素的降解。然而，另一类β-内酰胺酶即金属β-内酰胺酶（MBLs），其作用机制与丝氨酸-β-内酰胺酶不同，且尚无MBLs抑制剂进入临床使用阶段。表达MBLs的细菌对人类健康构成的威胁日益严重。本综述概述了发现MBLs抑制剂所采用的各种方法，重点介绍了不同化学类别的抑制剂。讨论了近期的进展，特别是新的筛选方法和强效MBLs抑制剂的合理设计。
