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Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors
Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complemen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359591/ https://www.ncbi.nlm.nih.gov/pubmed/30658415 http://dx.doi.org/10.3390/molecules24020327 |
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author | Espinosa-Valdés, Mariana Paola Borbolla-Alvarez, Sara Delgado-Espinosa, Ana Elena Sánchez-Tejeda, Juan Francisco Cerón-Nava, Anabelle Quintana-Romero, Osvaldo Javier Ariza-Castolo, Armando García-Del Río, Diego Fernando Loza-Mejía, Marco A. |
author_facet | Espinosa-Valdés, Mariana Paola Borbolla-Alvarez, Sara Delgado-Espinosa, Ana Elena Sánchez-Tejeda, Juan Francisco Cerón-Nava, Anabelle Quintana-Romero, Osvaldo Javier Ariza-Castolo, Armando García-Del Río, Diego Fernando Loza-Mejía, Marco A. |
author_sort | Espinosa-Valdés, Mariana Paola |
collection | PubMed |
description | Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins. |
format | Online Article Text |
id | pubmed-6359591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63595912019-02-06 Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors Espinosa-Valdés, Mariana Paola Borbolla-Alvarez, Sara Delgado-Espinosa, Ana Elena Sánchez-Tejeda, Juan Francisco Cerón-Nava, Anabelle Quintana-Romero, Osvaldo Javier Ariza-Castolo, Armando García-Del Río, Diego Fernando Loza-Mejía, Marco A. Molecules Article Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins. MDPI 2019-01-17 /pmc/articles/PMC6359591/ /pubmed/30658415 http://dx.doi.org/10.3390/molecules24020327 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 Espinosa-Valdés, Mariana Paola Borbolla-Alvarez, Sara Delgado-Espinosa, Ana Elena Sánchez-Tejeda, Juan Francisco Cerón-Nava, Anabelle Quintana-Romero, Osvaldo Javier Ariza-Castolo, Armando García-Del Río, Diego Fernando Loza-Mejía, Marco A. Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title | Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title_full | Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title_fullStr | Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title_full_unstemmed | Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title_short | Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors |
title_sort | synthesis, in silico, and in vitro evaluation of long chain alkyl amides from 2-amino-4-quinolone derivatives as biofilm inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359591/ https://www.ncbi.nlm.nih.gov/pubmed/30658415 http://dx.doi.org/10.3390/molecules24020327 |
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