Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783392295792410624
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
work_keys_str_mv AT espinosavaldesmarianapaola synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT borbollaalvarezsara synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT delgadoespinosaanaelena synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT sancheztejedajuanfrancisco synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT ceronnavaanabelle synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT quintanaromeroosvaldojavier synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT arizacastoloarmando synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT garciadelriodiegofernando synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors
AT lozamejiamarcoa synthesisinsilicoandinvitroevaluationoflongchainalkylamidesfrom2amino4quinolonederivativesasbiofilminhibitors