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Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents
In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently repo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557985/ https://www.ncbi.nlm.nih.gov/pubmed/28811659 http://dx.doi.org/10.1038/s41598-017-08749-6 |
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author | Zamperini, C. Maccari, G. Deodato, D. Pasero, C. D’Agostino, I. Orofino, F. De Luca, F. Dreassi, E. Docquier, J. D. Botta, M. |
author_facet | Zamperini, C. Maccari, G. Deodato, D. Pasero, C. D’Agostino, I. Orofino, F. De Luca, F. Dreassi, E. Docquier, J. D. Botta, M. |
author_sort | Zamperini, C. |
collection | PubMed |
description | In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently reported the identification of a series of linear guanidine derivatives and their antibacterial properties. A batch of a promising candidate for optimization studies (compound 1) turned out to be a mixture containing two unknown species with a better biological activity than the pure compound. This serendipitous discovery led us to investigate the chemical nature of the unknown components of the mixture. Through MS analysis coupled with design and synthesis we found that the components were spontaneously generated oligomers of the original compound. Preliminary biological evaluations eventually confirmed the broad-spectrum antibacterial activity of this new family of molecules. Interestingly the symmetric dimeric derivative (2) exhibited the best profile and it was selected as lead compound for further studies. |
format | Online Article Text |
id | pubmed-5557985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55579852017-08-18 Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents Zamperini, C. Maccari, G. Deodato, D. Pasero, C. D’Agostino, I. Orofino, F. De Luca, F. Dreassi, E. Docquier, J. D. Botta, M. Sci Rep Article In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently reported the identification of a series of linear guanidine derivatives and their antibacterial properties. A batch of a promising candidate for optimization studies (compound 1) turned out to be a mixture containing two unknown species with a better biological activity than the pure compound. This serendipitous discovery led us to investigate the chemical nature of the unknown components of the mixture. Through MS analysis coupled with design and synthesis we found that the components were spontaneously generated oligomers of the original compound. Preliminary biological evaluations eventually confirmed the broad-spectrum antibacterial activity of this new family of molecules. Interestingly the symmetric dimeric derivative (2) exhibited the best profile and it was selected as lead compound for further studies. Nature Publishing Group UK 2017-08-15 /pmc/articles/PMC5557985/ /pubmed/28811659 http://dx.doi.org/10.1038/s41598-017-08749-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zamperini, C. Maccari, G. Deodato, D. Pasero, C. D’Agostino, I. Orofino, F. De Luca, F. Dreassi, E. Docquier, J. D. Botta, M. Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title | Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title_full | Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title_fullStr | Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title_full_unstemmed | Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title_short | Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
title_sort | identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557985/ https://www.ncbi.nlm.nih.gov/pubmed/28811659 http://dx.doi.org/10.1038/s41598-017-08749-6 |
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