Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition

Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an...

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Main Authors: Zafar Iqbal, Jian Sun, Haikang Yang, Jingwen Ji, Lili He, Lijuan Zhai, Jinbo Ji, Pengjuan Zhou, Dong Tang, Yangxiu Mu, Lin Wang, Zhixiang Yang
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/12/3832
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author Zafar Iqbal
Jian Sun
Haikang Yang
Jingwen Ji
Lili He
Lijuan Zhai
Jinbo Ji
Pengjuan Zhou
Dong Tang
Yangxiu Mu
Lin Wang
Zhixiang Yang
author_facet Zafar Iqbal
Jian Sun
Haikang Yang
Jingwen Ji
Lili He
Lijuan Zhai
Jinbo Ji
Pengjuan Zhou
Dong Tang
Yangxiu Mu
Lin Wang
Zhixiang Yang
author_sort Zafar Iqbal
collection DOAJ
description Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first β-lactamase inhibitor (BLI), clavulanic acid. Over the years, β-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D β-lactamases. Boronic acids have shown promise in coping with Ambler class B β-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- β-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.
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spelling doaj.art-029785a3f66c462296c76f736aebb7282023-11-23T18:12:04ZengMDPI AGMolecules1420-30492022-06-012712383210.3390/molecules27123832Recent Developments to Cope the Antibacterial Resistance via β-Lactamase InhibitionZafar Iqbal0Jian Sun1Haikang Yang2Jingwen Ji3Lili He4Lijuan Zhai5Jinbo Ji6Pengjuan Zhou7Dong Tang8Yangxiu Mu9Lin Wang10Zhixiang Yang11Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaNingxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, ChinaAntibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first β-lactamase inhibitor (BLI), clavulanic acid. Over the years, β-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D β-lactamases. Boronic acids have shown promise in coping with Ambler class B β-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- β-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.https://www.mdpi.com/1420-3049/27/12/3832antibacterial resistanceβ-lactamase inhibitordiazabicyclooctaneboronic acidsavibactamrelebactam
spellingShingle Zafar Iqbal
Jian Sun
Haikang Yang
Jingwen Ji
Lili He
Lijuan Zhai
Jinbo Ji
Pengjuan Zhou
Dong Tang
Yangxiu Mu
Lin Wang
Zhixiang Yang
Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
Molecules
antibacterial resistance
β-lactamase inhibitor
diazabicyclooctane
boronic acids
avibactam
relebactam
title Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
title_full Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
title_fullStr Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
title_full_unstemmed Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
title_short Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
title_sort recent developments to cope the antibacterial resistance via β lactamase inhibition
topic antibacterial resistance
β-lactamase inhibitor
diazabicyclooctane
boronic acids
avibactam
relebactam
url https://www.mdpi.com/1420-3049/27/12/3832
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