SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Med Res Rev. 2018 Mar;38(2):426-503. doi: 10.1002/med.21443. Epub 2017 Aug 16.
Due to the widespread emergence of resistant bacterial strains, an urgent need for the development of new antibacterial agents with novel modes of action has emerged. The discovery of naturally occurring monocyclic β-lactams in the late 1970s, mainly active against aerobic Gram-negative bacteria, has introduced a new approach in the design and development of novel antibacterial β-lactam agents. The main goal was the derivatization of the azetidin-2-one core in order to improve their antibacterial potency, broaden their spectrum of activity, and enhance their β-lactamase stability. In that respect, our review covers the updates in the field of monocyclic β-lactam antibiotics during the last three decades, taking into account an extensive collection of references. An overview of the relationships between the structural features of these monocyclic β-lactams, classified according to their N-substituent, and the associated antibacterial or β-lactamase inhibitory activities is provided. The different paragraphs disclose a number of well-established classes of compounds, such as monobactams, monosulfactams, monocarbams, monophosphams, nocardicins, as well as other known representative classes. Moreover, this review draws attention to some less common but, nevertheless, possibly important types of monocyclic β-lactams and concludes by highlighting the recent developments on siderophore-conjugated classes of monocyclic β-lactams.
由于耐药菌株的广泛出现，人们迫切需要开发具有新型作用模式的新型抗菌剂。20 世纪 70 年代末发现的天然单环β-内酰胺主要对需氧革兰氏阴性菌有活性，为设计和开发新型抗菌β-内酰胺药物提供了一种新方法。主要目标是对氮杂环丁酮核心进行衍生化，以提高其抗菌效力、扩大其活性谱并增强其β-内酰胺酶稳定性。在这方面，我们的综述涵盖了过去三十年中单环β-内酰胺抗生素领域的最新进展，考虑了广泛的参考文献。概述了根据 N-取代基分类的这些单环β-内酰胺的结构特征与相关的抗菌或β-内酰胺酶抑制活性之间的关系。不同的段落揭示了一些已确立的化合物类别，如单酰胺类、单磺酰胺类、单氨基甲酸酯类、单磷酸酯类、诺卡霉素类以及其他已知的代表性类别。此外，本综述还提请注意一些不太常见但可能很重要的单环β-内酰胺类型，并通过强调最近关于铁载体偶联单环β-内酰胺类的发展来结束本文。
