Cargando…

Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1

The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of β-lactam antibiotics. Infections caused by some bacteria which secrete metallo-β-lactamases (enzymes that inactivate β-lactam antibiotics) are increasingly prevalent and have become a major world...

Descripción completa

Detalles Bibliográficos
Autores principales: Khalili Arjomandi, Omid, Kavoosi, Mahboubeh, Adibi, Hadi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853707/
https://www.ncbi.nlm.nih.gov/pubmed/31401901
http://dx.doi.org/10.1080/14756366.2019.1651314
_version_ 1784653284346167296
author Khalili Arjomandi, Omid
Kavoosi, Mahboubeh
Adibi, Hadi
author_facet Khalili Arjomandi, Omid
Kavoosi, Mahboubeh
Adibi, Hadi
author_sort Khalili Arjomandi, Omid
collection PubMed
description The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of β-lactam antibiotics. Infections caused by some bacteria which secrete metallo-β-lactamases (enzymes that inactivate β-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to β-lactam antibiotics and MBL-inhibitor/β-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-β-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a–2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a–k shows the potent inhibitory effects against metallo-β-lactamase (IMP-1) with the range of K(ic) values of 1.04–4.77 µM, they are not as potent as the candidate inhibitor.
format Online
Article
Text
id pubmed-8853707
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-88537072022-02-18 Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1 Khalili Arjomandi, Omid Kavoosi, Mahboubeh Adibi, Hadi J Enzyme Inhib Med Chem Original Article The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of β-lactam antibiotics. Infections caused by some bacteria which secrete metallo-β-lactamases (enzymes that inactivate β-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to β-lactam antibiotics and MBL-inhibitor/β-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-β-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a–2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a–k shows the potent inhibitory effects against metallo-β-lactamase (IMP-1) with the range of K(ic) values of 1.04–4.77 µM, they are not as potent as the candidate inhibitor. Taylor & Francis 2019-08-11 /pmc/articles/PMC8853707/ /pubmed/31401901 http://dx.doi.org/10.1080/14756366.2019.1651314 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Khalili Arjomandi, Omid
Kavoosi, Mahboubeh
Adibi, Hadi
Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title_full Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title_fullStr Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title_full_unstemmed Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title_short Synthesis and enzyme-based evaluation of analogues L-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
title_sort synthesis and enzyme-based evaluation of analogues l-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase imp-1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853707/
https://www.ncbi.nlm.nih.gov/pubmed/31401901
http://dx.doi.org/10.1080/14756366.2019.1651314
work_keys_str_mv AT khaliliarjomandiomid synthesisandenzymebasedevaluationofanaloguesltyrosinethiolcarboxylicacidinhibitorofmetalloblactamaseimp1
AT kavoosimahboubeh synthesisandenzymebasedevaluationofanaloguesltyrosinethiolcarboxylicacidinhibitorofmetalloblactamaseimp1
AT adibihadi synthesisandenzymebasedevaluationofanaloguesltyrosinethiolcarboxylicacidinhibitorofmetalloblactamaseimp1