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Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus
The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin (1) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912027/ https://www.ncbi.nlm.nih.gov/pubmed/35268604 http://dx.doi.org/10.3390/molecules27051504 |
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author | Hutchins, Mark Bovill, Richard A. Stephens, Peter J. Brazier, John A. Osborn, Helen M. I. |
author_facet | Hutchins, Mark Bovill, Richard A. Stephens, Peter J. Brazier, John A. Osborn, Helen M. I. |
author_sort | Hutchins, Mark |
collection | PubMed |
description | The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin (1) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans-linked (3a-e) and cis-linked (7a,b) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives (3a-e, 7a,b) were examined for potency against eight strains of S. aureus, four of which were methicillin-resistant. Although less potent than free nadifloxacin (1), the α-L-arabinofuransoside (3a) was effective against all strains that were tested (minimum inhibitory concentrations of 1–8 μg/mL compared to 0.1–0.25 μg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin (1), raising the prospect of its use in oral applications. |
format | Online Article Text |
id | pubmed-8912027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89120272022-03-11 Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus Hutchins, Mark Bovill, Richard A. Stephens, Peter J. Brazier, John A. Osborn, Helen M. I. Molecules Article The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin (1) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans-linked (3a-e) and cis-linked (7a,b) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives (3a-e, 7a,b) were examined for potency against eight strains of S. aureus, four of which were methicillin-resistant. Although less potent than free nadifloxacin (1), the α-L-arabinofuransoside (3a) was effective against all strains that were tested (minimum inhibitory concentrations of 1–8 μg/mL compared to 0.1–0.25 μg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin (1), raising the prospect of its use in oral applications. MDPI 2022-02-23 /pmc/articles/PMC8912027/ /pubmed/35268604 http://dx.doi.org/10.3390/molecules27051504 Text en © 2022 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 | Article Hutchins, Mark Bovill, Richard A. Stephens, Peter J. Brazier, John A. Osborn, Helen M. I. Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title | Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title_full | Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title_fullStr | Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title_full_unstemmed | Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title_short | Glycosides of Nadifloxacin—Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus |
title_sort | glycosides of nadifloxacin—synthesis and antibacterial activities against methicillin-resistant staphylococcus aureus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912027/ https://www.ncbi.nlm.nih.gov/pubmed/35268604 http://dx.doi.org/10.3390/molecules27051504 |
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