Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Lili, Shao, Liping, Li, Jing, Cui, Haifeng, Li, Bing, Zhou, Xuzheng, Lv, Pengyue, Zhang, Jiyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783417985806893056
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
work_keys_str_mv AT liulili synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT shaoliping synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT lijing synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT cuihaifeng synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT libing synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT zhouxuzheng synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT lvpengyue synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids
AT zhangjiyu synthesisantibacterialactivitiesmodeofactionandacutetoxicitystudiesofnewoxazolidinonefluoroquinolonehybrids