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Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins

A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G(+)/G(−) pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug baloflox...

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Autores principales: Hong, Ge, Li, Weitian, Mao, Lina, Wang, Jiawen, Liu, Tianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437215/
https://www.ncbi.nlm.nih.gov/pubmed/36059868
http://dx.doi.org/10.3389/fchem.2022.963442
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author Hong, Ge
Li, Weitian
Mao, Lina
Wang, Jiawen
Liu, Tianjun
author_facet Hong, Ge
Li, Weitian
Mao, Lina
Wang, Jiawen
Liu, Tianjun
author_sort Hong, Ge
collection PubMed
description A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G(+)/G(−) pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug balofloxacin against MRSA and P. aeruginosa (MIC values of 0.0195 and 0.039 μg/ml for 2-e, 0.039 and 0.078 μg/ml for each of 3-e and 4-e, respectively). Analysis of the time-dependent antibacterial effect of compound 2-e toward MRSA showed that in the early logarithmic growth phase, bactericidal effects occurred, while in the late logarithmic growth phase, bacterial inhibition occurred because of concentration effects and possibly the development of drug resistance. Compound 2-e exhibited low toxicity toward normal mammalian cell lines 3T3 and L-02 and tumor cell lines A549, H520, BEL-7402, and MCF-7. The compound was not hemolytic. Atomic force microscopy (AFM) revealed that compound 2-e could effectively destroy the membrane and wall of MRSA cells, resulting in the outflow of the cellular contents. Docking studies indicated the good binding profile of these compounds toward DNA gyrase and topoisomerase IV. ADMET’s prediction showed that most of the synthesized compounds followed Lipinski’s “rule of five” and possessed good drug-like properties. Our data suggested that compound 2-e exhibited potent anti-MRSA activity and is worthy of further investigation.
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spelling pubmed-94372152022-09-03 Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins Hong, Ge Li, Weitian Mao, Lina Wang, Jiawen Liu, Tianjun Front Chem Chemistry A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G(+)/G(−) pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug balofloxacin against MRSA and P. aeruginosa (MIC values of 0.0195 and 0.039 μg/ml for 2-e, 0.039 and 0.078 μg/ml for each of 3-e and 4-e, respectively). Analysis of the time-dependent antibacterial effect of compound 2-e toward MRSA showed that in the early logarithmic growth phase, bactericidal effects occurred, while in the late logarithmic growth phase, bacterial inhibition occurred because of concentration effects and possibly the development of drug resistance. Compound 2-e exhibited low toxicity toward normal mammalian cell lines 3T3 and L-02 and tumor cell lines A549, H520, BEL-7402, and MCF-7. The compound was not hemolytic. Atomic force microscopy (AFM) revealed that compound 2-e could effectively destroy the membrane and wall of MRSA cells, resulting in the outflow of the cellular contents. Docking studies indicated the good binding profile of these compounds toward DNA gyrase and topoisomerase IV. ADMET’s prediction showed that most of the synthesized compounds followed Lipinski’s “rule of five” and possessed good drug-like properties. Our data suggested that compound 2-e exhibited potent anti-MRSA activity and is worthy of further investigation. Frontiers Media S.A. 2022-08-19 /pmc/articles/PMC9437215/ /pubmed/36059868 http://dx.doi.org/10.3389/fchem.2022.963442 Text en Copyright © 2022 Hong, Li, Mao, Wang and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Hong, Ge
Li, Weitian
Mao, Lina
Wang, Jiawen
Liu, Tianjun
Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title_full Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title_fullStr Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title_full_unstemmed Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title_short Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins
title_sort synthesis and antibacterial activity evaluation of n (7) position-modified balofloxacins
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437215/
https://www.ncbi.nlm.nih.gov/pubmed/36059868
http://dx.doi.org/10.3389/fchem.2022.963442
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