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Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids
To combat bacterial resistance, a series of new oxazolidinone-fluoroquinolone hybrids have been synthesized and characterized. All synthetic hybrids were preliminarily evaluated for their in vitro antibacterial activities against 6 standard strains and 3 clinical isolates. The majority of hybrids di...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514978/ https://www.ncbi.nlm.nih.gov/pubmed/31027311 http://dx.doi.org/10.3390/molecules24081641 |
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author | Liu, Lili Shao, Liping Li, Jing Cui, Haifeng Li, Bing Zhou, Xuzheng Lv, Pengyue Zhang, Jiyu |
author_facet | Liu, Lili Shao, Liping Li, Jing Cui, Haifeng Li, Bing Zhou, Xuzheng Lv, Pengyue Zhang, Jiyu |
author_sort | Liu, Lili |
collection | PubMed |
description | To combat bacterial resistance, a series of new oxazolidinone-fluoroquinolone hybrids have been synthesized and characterized. All synthetic hybrids were preliminarily evaluated for their in vitro antibacterial activities against 6 standard strains and 3 clinical isolates. The majority of hybrids displayed excellent activities against Gram-positive bacteria, but limited activities against Gram-negative bacteria. Hybrids OBP-4 and OBP-5 were found to be the most promising compounds. Further, in vitro antibacterial activities, mode of action and acute toxicity in mice of hybrids OBP-4 and OBP-5 were investigated. Hybrids OBP-4 and OBP-5 exhibited potent activities against Gram-positive bacteria, including drug-resistant strains. Correspondingly, studies on the mode of action of hybrids OBP-4 and OBP-5 indicated a strong inhibitory activity on protein synthesis by binding the active site of 50S subunit, but a weak inhibitory action on DNA synthesis. In addition, LD(50) values of hybrids OBP-4 and OBP-5 in the acute oral toxicity were larger than 2000 mg/kg, suggesting a good safety profile. |
format | Online Article Text |
id | pubmed-6514978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65149782019-05-30 Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids Liu, Lili Shao, Liping Li, Jing Cui, Haifeng Li, Bing Zhou, Xuzheng Lv, Pengyue Zhang, Jiyu Molecules Article To combat bacterial resistance, a series of new oxazolidinone-fluoroquinolone hybrids have been synthesized and characterized. All synthetic hybrids were preliminarily evaluated for their in vitro antibacterial activities against 6 standard strains and 3 clinical isolates. The majority of hybrids displayed excellent activities against Gram-positive bacteria, but limited activities against Gram-negative bacteria. Hybrids OBP-4 and OBP-5 were found to be the most promising compounds. Further, in vitro antibacterial activities, mode of action and acute toxicity in mice of hybrids OBP-4 and OBP-5 were investigated. Hybrids OBP-4 and OBP-5 exhibited potent activities against Gram-positive bacteria, including drug-resistant strains. Correspondingly, studies on the mode of action of hybrids OBP-4 and OBP-5 indicated a strong inhibitory activity on protein synthesis by binding the active site of 50S subunit, but a weak inhibitory action on DNA synthesis. In addition, LD(50) values of hybrids OBP-4 and OBP-5 in the acute oral toxicity were larger than 2000 mg/kg, suggesting a good safety profile. MDPI 2019-04-25 /pmc/articles/PMC6514978/ /pubmed/31027311 http://dx.doi.org/10.3390/molecules24081641 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Lili Shao, Liping Li, Jing Cui, Haifeng Li, Bing Zhou, Xuzheng Lv, Pengyue Zhang, Jiyu Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title | Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title_full | Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title_fullStr | Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title_full_unstemmed | Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title_short | Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids |
title_sort | synthesis, antibacterial activities, mode of action and acute toxicity studies of new oxazolidinone-fluoroquinolone hybrids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514978/ https://www.ncbi.nlm.nih.gov/pubmed/31027311 http://dx.doi.org/10.3390/molecules24081641 |
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