β-内酰胺酶抑制剂的研究进展

Research progress of b-lactamase inhibitors

关键词:  β-内酰胺酶  酶抑制剂  细菌耐药

Key words:  β-lactamase  Inhibitors  Bacterial resistance

摘要:

β-内酰胺酶抑制剂在对抗β-内酰胺酶耐药菌感染中发挥着重要作用，一直是药物化学领域的研究热点，但β-内酰胺酶变异体多元化及不利突变在减缓了新型抑制剂的发展进程。诸多国内外相关文献在深入了解β-内酰胺酶水解机制及活性位点关键氨基酸作用特点的基础上，通过对已有化合物进行结构修饰或基于片段设计来筛选新的β-内酰胺酶抑制剂。本文详细介绍了β-内酰胺酶抑制剂的研究进展，旨在为进一步深入开展以增强化合物与酶关键氨基酸互作为基础的创新药物筛选提供帮助。

Abstract:

β-lactamase inhibitors (βLIs) have played an important role in combatting β-lactam-resistant bacteria, which has been a hotspot in the field of medicinal chemistry , but their development has diminished with the evolution of diverse and deleterious varieties of β-lactamases. With deep understanding of the β-lactamase hydrolysis mechanism and the function of the key amino acid of its active sites, varieties of literatures aimed at designing and screening active compounds by structurally modifying the existing compounds or fragment-based dsicovery were reported, meanwhile several novel enzyme inactivation mechanisms have been also reported. Herein, the research progress of serine- and metallo-β-lactamases inhibitors was introduced in detail, in order to provide systematic information for further development of new drug based on enhancing its interaction with the key amino acids of the β-lactamase enzyme.