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针对新德里金属β-内酰胺酶(NDM-1)的抑制剂设计研究

Efforts towards the inhibitor design for New Delhi metallo-beta-lactamase (NDM-1).

作者信息

Nagulapalli Venkata Kalyan C, Ellebrecht Morgan, Tripathi Siddharth K

机构信息

St. Louis College of Pharmacy, University of Health Sciences and Pharmacy, St. Louis, MO, 63110, USA.

St. Louis College of Pharmacy, University of Health Sciences and Pharmacy, St. Louis, MO, 63110, USA.

出版信息

Eur J Med Chem. 2021 Dec 5;225:113747. doi: 10.1016/j.ejmech.2021.113747. Epub 2021 Aug 5.

Abstract

Antimicrobial stewardship is imperative when treating bacterial infections because the misuse and overuse of antibiotics have caused pathogens to develop life-threatening resistance mechanisms. The New Delhi metallo-beta-lactamase (NDM-1) is one of many enzymes that enable bacterial resistance. NDM-1 is a more recently discovered beta-lactamase with the ability to inactivate a wide range of beta-lactam antibiotics. Multiple NDM-1 inhibitors have been designed and tested; however, due to the complexity of the NDM-1 active site, there is currently no inhibitor on the market. Consequently, an infection caused by bacteria possessing the gene for the NDM-1 enzyme is a serious and potentially fatal complication. An abundance of research has been invested over the past decade in search of an NDM-1 inhibitor. This review aims to summarize various NDM-1 inhibitor designs that have been developed in recent years.

摘要

在治疗细菌感染时,抗菌药物管理至关重要,因为抗生素的滥用和过度使用已导致病原体形成危及生命的耐药机制。新德里金属β-内酰胺酶(NDM-1)是众多使细菌产生耐药性的酶之一。NDM-1是一种较新发现的β-内酰胺酶,能够使多种β-内酰胺抗生素失活。多种NDM-1抑制剂已被设计和测试;然而,由于NDM-1活性位点的复杂性,目前市场上尚无抑制剂。因此,由携带NDM-1酶基因的细菌引起的感染是一种严重且可能致命的并发症。在过去十年中,人们投入了大量研究来寻找NDM-1抑制剂。本综述旨在总结近年来开发的各种NDM-1抑制剂设计。

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