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DNA Gyrase as a Target for Quinolones
Bacterial DNA gyrase is a type II topoisomerase that can introduce negative supercoils to DNA substrates and is a clinically-relevant target for the development of new antibacterials. DNA gyrase is one of the primary targets of quinolones, broad-spectrum antibacterial agents and are used as a first-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953508/ https://www.ncbi.nlm.nih.gov/pubmed/36830908 http://dx.doi.org/10.3390/biomedicines11020371 |
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author | Spencer, Angela C. Panda, Siva S. |
author_facet | Spencer, Angela C. Panda, Siva S. |
author_sort | Spencer, Angela C. |
collection | PubMed |
description | Bacterial DNA gyrase is a type II topoisomerase that can introduce negative supercoils to DNA substrates and is a clinically-relevant target for the development of new antibacterials. DNA gyrase is one of the primary targets of quinolones, broad-spectrum antibacterial agents and are used as a first-line drug for various types of infections. However, currently used quinolones are becoming less effective due to drug resistance. Common resistance comes in the form of mutation in enzyme targets, with this type being the most clinically relevant. Additional mechanisms, conducive to quinolone resistance, are arbitrated by chromosomal mutations and/or plasmid-gene uptake that can alter quinolone cellular concentration and interaction with the target, or affect drug metabolism. Significant synthetic strategies have been employed to modify the quinolone scaffold and/or develop novel quinolones to overcome the resistance problem. This review discusses the development of quinolone antibiotics targeting DNA gyrase to overcome bacterial resistance and reduce toxicity. Moreover, structural activity relationship (SAR) data included in this review could be useful for the development of future generations of quinolone antibiotics. |
format | Online Article Text |
id | pubmed-9953508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99535082023-02-25 DNA Gyrase as a Target for Quinolones Spencer, Angela C. Panda, Siva S. Biomedicines Review Bacterial DNA gyrase is a type II topoisomerase that can introduce negative supercoils to DNA substrates and is a clinically-relevant target for the development of new antibacterials. DNA gyrase is one of the primary targets of quinolones, broad-spectrum antibacterial agents and are used as a first-line drug for various types of infections. However, currently used quinolones are becoming less effective due to drug resistance. Common resistance comes in the form of mutation in enzyme targets, with this type being the most clinically relevant. Additional mechanisms, conducive to quinolone resistance, are arbitrated by chromosomal mutations and/or plasmid-gene uptake that can alter quinolone cellular concentration and interaction with the target, or affect drug metabolism. Significant synthetic strategies have been employed to modify the quinolone scaffold and/or develop novel quinolones to overcome the resistance problem. This review discusses the development of quinolone antibiotics targeting DNA gyrase to overcome bacterial resistance and reduce toxicity. Moreover, structural activity relationship (SAR) data included in this review could be useful for the development of future generations of quinolone antibiotics. MDPI 2023-01-27 /pmc/articles/PMC9953508/ /pubmed/36830908 http://dx.doi.org/10.3390/biomedicines11020371 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Spencer, Angela C. Panda, Siva S. DNA Gyrase as a Target for Quinolones |
title | DNA Gyrase as a Target for Quinolones |
title_full | DNA Gyrase as a Target for Quinolones |
title_fullStr | DNA Gyrase as a Target for Quinolones |
title_full_unstemmed | DNA Gyrase as a Target for Quinolones |
title_short | DNA Gyrase as a Target for Quinolones |
title_sort | dna gyrase as a target for quinolones |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953508/ https://www.ncbi.nlm.nih.gov/pubmed/36830908 http://dx.doi.org/10.3390/biomedicines11020371 |
work_keys_str_mv | AT spencerangelac dnagyraseasatargetforquinolones AT pandasivas dnagyraseasatargetforquinolones |