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Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells
A series of cationic conjugated oligoelectrolytes (COEs) was designed to understand how variations in molecular dimensions impact the relative activity against bacteria and mammalian cells. These COEs kept a consistent distyrylbenzene framework but differed in the length of linker between the core a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163332/ https://www.ncbi.nlm.nih.gov/pubmed/34123085 http://dx.doi.org/10.1039/d0sc03679j |
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author | Limwongyut, Jakkarin Nie, Chenyao Moreland, Alex S. Bazan, Guillermo C. |
author_facet | Limwongyut, Jakkarin Nie, Chenyao Moreland, Alex S. Bazan, Guillermo C. |
author_sort | Limwongyut, Jakkarin |
collection | PubMed |
description | A series of cationic conjugated oligoelectrolytes (COEs) was designed to understand how variations in molecular dimensions impact the relative activity against bacteria and mammalian cells. These COEs kept a consistent distyrylbenzene framework but differed in the length of linker between the core and the cationic site and the length of substitute on the quaternary ammonium functioned group. Their antimicrobial efficacy, mammalian cell cytotoxicity, hemolytic activity, and cell association were determined. We find that hydrophobicity is a factor that controls the degree of COE association to cells, but in vitro efficacy and cytotoxicity depend on more subtle structural features. COE2-3C-C4butyl was found to be the optimal structure with a minimum inhibitory concentration (MIC) of 4 μg mL(−1) against E. coli K12, low cytotoxicity against HepG2 cells and negligible hemolysis of red blood cells, even at 1024 μg mL(−1). A time-kill kinetics study of COE2-3C-C4butyl against E. coli K12 demonstrates bactericidal activity. These findings provide the first systematic investigation of how COEs may be modulated to achieve low mammalian cell cytotoxicity with the long-range perspective of finding candidates suitable for developing a broad-spectrum antimicrobial agent. |
format | Online Article Text |
id | pubmed-8163332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-81633322021-06-11 Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells Limwongyut, Jakkarin Nie, Chenyao Moreland, Alex S. Bazan, Guillermo C. Chem Sci Chemistry A series of cationic conjugated oligoelectrolytes (COEs) was designed to understand how variations in molecular dimensions impact the relative activity against bacteria and mammalian cells. These COEs kept a consistent distyrylbenzene framework but differed in the length of linker between the core and the cationic site and the length of substitute on the quaternary ammonium functioned group. Their antimicrobial efficacy, mammalian cell cytotoxicity, hemolytic activity, and cell association were determined. We find that hydrophobicity is a factor that controls the degree of COE association to cells, but in vitro efficacy and cytotoxicity depend on more subtle structural features. COE2-3C-C4butyl was found to be the optimal structure with a minimum inhibitory concentration (MIC) of 4 μg mL(−1) against E. coli K12, low cytotoxicity against HepG2 cells and negligible hemolysis of red blood cells, even at 1024 μg mL(−1). A time-kill kinetics study of COE2-3C-C4butyl against E. coli K12 demonstrates bactericidal activity. These findings provide the first systematic investigation of how COEs may be modulated to achieve low mammalian cell cytotoxicity with the long-range perspective of finding candidates suitable for developing a broad-spectrum antimicrobial agent. The Royal Society of Chemistry 2020-07-24 /pmc/articles/PMC8163332/ /pubmed/34123085 http://dx.doi.org/10.1039/d0sc03679j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Limwongyut, Jakkarin Nie, Chenyao Moreland, Alex S. Bazan, Guillermo C. Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title | Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title_full | Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title_fullStr | Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title_full_unstemmed | Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title_short | Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
title_sort | molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163332/ https://www.ncbi.nlm.nih.gov/pubmed/34123085 http://dx.doi.org/10.1039/d0sc03679j |
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