A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents

Cationic and non-peptide small molecules containing a total of six positive charges arranged on one side and a long aliphatic tail on the other have been synthesized and tested against Gram-positive and Gram-negative bacteria. The positive charges have been contributed by two aminophenol residues. T...

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Detalles Bibliográficos
Autores: Jiménez, Aranza, García, Pablo, Puente-Secades, Sofía de la, Madrona, Andrés, Camarasa Rius, María José, Peréz-Pérez, María-Jesús, Quintela Fernández, José Carlos, García del Portillo, Francisco, San-Félix, Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/167935
Acceso en línea:http://hdl.handle.net/10261/167935
Access Level:acceso abierto
Palabra clave:Antimicrobial agents
Antibiotic resistance
Antimicrobial peptides
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spelling A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial AgentsJiménez, AranzaGarcía, PabloPuente-Secades, Sofía de laMadrona, AndrésCamarasa Rius, María JoséPeréz-Pérez, María-JesúsQuintela Fernández, José CarlosGarcía del Portillo, FranciscoSan-Félix, AnaAntimicrobial agentsAntibiotic resistanceAntimicrobial peptidesCationic and non-peptide small molecules containing a total of six positive charges arranged on one side and a long aliphatic tail on the other have been synthesized and tested against Gram-positive and Gram-negative bacteria. The positive charges have been contributed by two aminophenol residues. These molecules have showed remarkable antimicrobial activity against Gram-positive bacteria including multidrug-resistant strains. Our structure–activity relationship studies demonstrated the importance of the length and flexibility of the hydrophobic tail for the antimicrobial activity. Importantly, these compounds are non-toxic to eukaryotic cells at the concentration affecting growth in bacteria, reflecting an acceptable margin of safety. The small size and easy synthetic accessibility of our molecules can be of interest for the further development of novel antimicrobials against Gram-positive bacterial pathogens, including multidrug-resistant strains.This research was funded by the Spanish “Plan Nacional de Cooperación Público-Privada, Subprograma INNPACTO” project number IPT-2012-0213 060000, cofinanced by the FEDER program (to J.-C.Q., F.G.-d.P, A.S.-F. and M.-J.P.-P.), “Ministerio de Economia, Industria y Competitividad, Gobierno de España” and “European Regional Development Funds” projects numbers SAF2015-64629-C2-1-R (MINECO/FEDER) (to A.S.-F., M.-J.C. and M.-J.P.-P.) and BIO2016-77639-P (MINECO/FEDER) (to F.G.-d.P.). The Spanish MEC/MINECO is also acknowledged for Garantía Juvenil contracts to A.J. and S.d.l.P.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Economía, Industria y Competitividad (España)European CommissionMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2018201820182018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/167935reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64629-C2-1-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-77639-Phttps://doi.org/10.3390/molecules23071513Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1679352026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
title A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
spellingShingle A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
Jiménez, Aranza
Antimicrobial agents
Antibiotic resistance
Antimicrobial peptides
title_short A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
title_full A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
title_fullStr A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
title_full_unstemmed A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
title_sort A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents
dc.creator.none.fl_str_mv Jiménez, Aranza
García, Pablo
Puente-Secades, Sofía de la
Madrona, Andrés
Camarasa Rius, María José
Peréz-Pérez, María-Jesús
Quintela Fernández, José Carlos
García del Portillo, Francisco
San-Félix, Ana
author Jiménez, Aranza
author_facet Jiménez, Aranza
García, Pablo
Puente-Secades, Sofía de la
Madrona, Andrés
Camarasa Rius, María José
Peréz-Pérez, María-Jesús
Quintela Fernández, José Carlos
García del Portillo, Francisco
San-Félix, Ana
author_role author
author2 García, Pablo
Puente-Secades, Sofía de la
Madrona, Andrés
Camarasa Rius, María José
Peréz-Pérez, María-Jesús
Quintela Fernández, José Carlos
García del Portillo, Francisco
San-Félix, Ana
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
European Commission
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Antimicrobial agents
Antibiotic resistance
Antimicrobial peptides
topic Antimicrobial agents
Antibiotic resistance
Antimicrobial peptides
description Cationic and non-peptide small molecules containing a total of six positive charges arranged on one side and a long aliphatic tail on the other have been synthesized and tested against Gram-positive and Gram-negative bacteria. The positive charges have been contributed by two aminophenol residues. These molecules have showed remarkable antimicrobial activity against Gram-positive bacteria including multidrug-resistant strains. Our structure–activity relationship studies demonstrated the importance of the length and flexibility of the hydrophobic tail for the antimicrobial activity. Importantly, these compounds are non-toxic to eukaryotic cells at the concentration affecting growth in bacteria, reflecting an acceptable margin of safety. The small size and easy synthetic accessibility of our molecules can be of interest for the further development of novel antimicrobials against Gram-positive bacterial pathogens, including multidrug-resistant strains.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/167935
url http://hdl.handle.net/10261/167935
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64629-C2-1-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-77639-P
https://doi.org/10.3390/molecules23071513
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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