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-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/371 |
| _version_ | 1827758455275913216 |
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| author | Angela C. Spencer Siva S. Panda |
| author_facet | Angela C. Spencer Siva S. Panda |
| author_sort | Angela C. Spencer |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T09:06:37Z |
| format | Article |
| id | doaj.art-0d6a744351d74613823791094d88ed2f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:06:37Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0d6a744351d74613823791094d88ed2f2023-11-16T19:17:15ZengMDPI AGBiomedicines2227-90592023-01-0111237110.3390/biomedicines11020371DNA Gyrase as a Target for QuinolonesAngela C. Spencer0Siva S. Panda1Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USADepartment of Chemistry and Physics, Augusta University, Augusta, GA 30912, USABacterial 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.https://www.mdpi.com/2227-9059/11/2/371quinolonesDNA gyrasemolecular dockingdrug developmentdrug-resistance |
| spellingShingle | Angela C. Spencer Siva S. Panda DNA Gyrase as a Target for Quinolones Biomedicines quinolones DNA gyrase molecular docking drug development drug-resistance |
| 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 | quinolones DNA gyrase molecular docking drug development drug-resistance |
| url | https://www.mdpi.com/2227-9059/11/2/371 |
| work_keys_str_mv | AT angelacspencer dnagyraseasatargetforquinolones AT sivaspanda dnagyraseasatargetforquinolones |