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针对 NDM-1 型金属β-内酰胺酶的潜在抑制剂:概述。

Potential Inhibitors Against NDM-1 Type Metallo-β-Lactamases: An Overview.

机构信息

Clinical Microbiology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Integrative Medicine, Jammu Tawi, India.

Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Integrative Medicine, Jammu Tawi, India.

出版信息

Microb Drug Resist. 2020 Dec;26(12):1568-1588. doi: 10.1089/mdr.2019.0315. Epub 2020 Jun 2.

Abstract

A new member of the class metallo-β-lactamase (MBL), New Delhi metallo-beta-lactamase 1 (NDM-1) has emerged recently as a leading threat to the treatment of infections that have spread in all major Gram-negative pathogens. The enzyme inactivates antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. This review provides information about NDM-1 spatial structure, potential features of the active site, and its mechanism of action. It also enlists the inhibitors/compounds/drugs against NDM-1 in various development phases. Understanding their mode of inhibition and the structure-activity relationship would be beneficial for development, synthesis, and even increasing biological efficacy of inhibitors, making them more promising drug candidates.

摘要

一种新的金属β-内酰胺酶(MBL)成员——新德里金属β-内酰胺酶 1(NDM-1)最近出现,成为所有主要革兰氏阴性病原体传播的感染治疗的主要威胁。该酶使碳青霉烯类抗生素失活,而碳青霉烯类抗生素是治疗抗生素耐药细菌感染的主要药物。本文综述了 NDM-1 的空间结构、活性位点的潜在特征及其作用机制。还列出了处于不同研发阶段的针对 NDM-1 的抑制剂/化合物/药物。了解它们的抑制模式和构效关系有助于抑制剂的开发、合成,甚至提高其生物效力,使它们成为更有前途的候选药物。

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