Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate

A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have mu...

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Autores principales: Zhang, Tingting, Wu, Jinwei, Chen, Shihong, Liu, Kaixiang, Lin, Yabin, Guo, Huiyuan, Liu, Mingliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270849/
https://www.ncbi.nlm.nih.gov/pubmed/24858269
http://dx.doi.org/10.3390/molecules19056822
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author Zhang, Tingting
Wu, Jinwei
Chen, Shihong
Liu, Kaixiang
Lin, Yabin
Guo, Huiyuan
Liu, Mingliang
author_facet Zhang, Tingting
Wu, Jinwei
Chen, Shihong
Liu, Kaixiang
Lin, Yabin
Guo, Huiyuan
Liu, Mingliang
author_sort Zhang, Tingting
collection PubMed
description A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32–7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39–23.13 mg/kg) which is 1.19–1.50 fold more active than the parent drug.
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spelling pubmed-62708492018-12-21 Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate Zhang, Tingting Wu, Jinwei Chen, Shihong Liu, Kaixiang Lin, Yabin Guo, Huiyuan Liu, Mingliang Molecules Article A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32–7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39–23.13 mg/kg) which is 1.19–1.50 fold more active than the parent drug. MDPI 2014-05-23 /pmc/articles/PMC6270849/ /pubmed/24858269 http://dx.doi.org/10.3390/molecules19056822 Text en © 2014 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhang, Tingting
Wu, Jinwei
Chen, Shihong
Liu, Kaixiang
Lin, Yabin
Guo, Huiyuan
Liu, Mingliang
Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title_full Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title_fullStr Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title_full_unstemmed Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title_short Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate
title_sort synthesis and antibacterial activity of amino acid and dipeptide prodrugs of imb-070593, a fluoroquinolone candidate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270849/
https://www.ncbi.nlm.nih.gov/pubmed/24858269
http://dx.doi.org/10.3390/molecules19056822
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