Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species

Autores
Saeed, Aamer; Bosch, María Alejandra; Bettiol, Marisa; Nossa González, Diana Lisseth; Erben, Mauricio Federico; Lamberti, Yanina Andrea
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis (CF). Infections dominated by non-fermentative Gram-negative bacilli are particularly difficult to treat and highlight an urgent need for the development of new class of agents to combat these infections. In this work, a small library comprising thiourea and guanidine derivatives with low molecular weight was designed; these derivatives were studied as antimicrobial agents against Gram-positive, Gram-negative, and a panel of drug-resistant clinical isolates recovered from patients with CF. One novel compound, a guanidine derivative bearing adamantane-1-carbonyl and 2-bromo-4,6-difluouro-phenyl substituents (H-BDF), showed potent bactericidal activity against the strains tested, at levels generally higher than those exhibited by tobramycin, ceftazimide and meropenem. The role that different substituents exert in the antimicrobial activity has been determined, highlighting the importance of the halo-phenyl group in the guanidine moiety. The new compound displays low levels of cytotoxicity against THP-1 and A549 cells with a selective index (SI) > 8 (patent application PCT/IB2017/054870, August 2017). Taken together, our results indicate that H-BDF can be considered as a promising antimicrobial agent.
Fil: Saeed, Aamer. Quaid-i-azam University; Pakistán
Fil: Bosch, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Bettiol, Marisa. Hospital de Niños Superiora Sor María Ludovica; Argentina
Fil: Nossa González, Diana Lisseth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Lamberti, Yanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Materia
Antimicrobials
Thioureas
Guanidines
Drug-resistant
Cystic fibrosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87543
Acceder
id CONICETDig_b6fed0e149fb876b7df3ef9ec19fa984
oai_identifier_str oai:ri.conicet.gov.ar:11336/87543
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial SpeciesSaeed, AamerBosch, María AlejandraBettiol, MarisaNossa González, Diana LissethErben, Mauricio FedericoLamberti, Yanina AndreaAntimicrobialsThioureasGuanidinesDrug-resistantCystic fibrosishttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis (CF). Infections dominated by non-fermentative Gram-negative bacilli are particularly difficult to treat and highlight an urgent need for the development of new class of agents to combat these infections. In this work, a small library comprising thiourea and guanidine derivatives with low molecular weight was designed; these derivatives were studied as antimicrobial agents against Gram-positive, Gram-negative, and a panel of drug-resistant clinical isolates recovered from patients with CF. One novel compound, a guanidine derivative bearing adamantane-1-carbonyl and 2-bromo-4,6-difluouro-phenyl substituents (H-BDF), showed potent bactericidal activity against the strains tested, at levels generally higher than those exhibited by tobramycin, ceftazimide and meropenem. The role that different substituents exert in the antimicrobial activity has been determined, highlighting the importance of the halo-phenyl group in the guanidine moiety. The new compound displays low levels of cytotoxicity against THP-1 and A549 cells with a selective index (SI) > 8 (patent application PCT/IB2017/054870, August 2017). Taken together, our results indicate that H-BDF can be considered as a promising antimicrobial agent.Fil: Saeed, Aamer. Quaid-i-azam University; PakistánFil: Bosch, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Bettiol, Marisa. Hospital de Niños Superiora Sor María Ludovica; ArgentinaFil: Nossa González, Diana Lisseth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Lamberti, Yanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaMolecular Diversity Preservation International2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87543Saeed, Aamer; Bosch, María Alejandra; Bettiol, Marisa; Nossa González, Diana Lisseth; Erben, Mauricio Federico; et al.; Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species; Molecular Diversity Preservation International; Molecules; 23; 5; 5-2018; 1158-11701420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23051158info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/5/1158info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:19:25Zoai:ri.conicet.gov.ar:11336/87543instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:19:26.09CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
title Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
spellingShingle Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
Saeed, Aamer
Antimicrobials
Thioureas
Guanidines
Drug-resistant
Cystic fibrosis
title_short Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
title_full Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
title_fullStr Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
title_full_unstemmed Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
title_sort Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
dc.creator.none.fl_str_mv Saeed, Aamer
Bosch, María Alejandra
Bettiol, Marisa
Nossa González, Diana Lisseth
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author Saeed, Aamer
author_facet Saeed, Aamer
Bosch, María Alejandra
Bettiol, Marisa
Nossa González, Diana Lisseth
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author_role author
author2 Bosch, María Alejandra
Bettiol, Marisa
Nossa González, Diana Lisseth
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Antimicrobials
Thioureas
Guanidines
Drug-resistant
Cystic fibrosis
topic Antimicrobials
Thioureas
Guanidines
Drug-resistant
Cystic fibrosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis (CF). Infections dominated by non-fermentative Gram-negative bacilli are particularly difficult to treat and highlight an urgent need for the development of new class of agents to combat these infections. In this work, a small library comprising thiourea and guanidine derivatives with low molecular weight was designed; these derivatives were studied as antimicrobial agents against Gram-positive, Gram-negative, and a panel of drug-resistant clinical isolates recovered from patients with CF. One novel compound, a guanidine derivative bearing adamantane-1-carbonyl and 2-bromo-4,6-difluouro-phenyl substituents (H-BDF), showed potent bactericidal activity against the strains tested, at levels generally higher than those exhibited by tobramycin, ceftazimide and meropenem. The role that different substituents exert in the antimicrobial activity has been determined, highlighting the importance of the halo-phenyl group in the guanidine moiety. The new compound displays low levels of cytotoxicity against THP-1 and A549 cells with a selective index (SI) > 8 (patent application PCT/IB2017/054870, August 2017). Taken together, our results indicate that H-BDF can be considered as a promising antimicrobial agent.
Fil: Saeed, Aamer. Quaid-i-azam University; Pakistán
Fil: Bosch, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Bettiol, Marisa. Hospital de Niños Superiora Sor María Ludovica; Argentina
Fil: Nossa González, Diana Lisseth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Lamberti, Yanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
description Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis (CF). Infections dominated by non-fermentative Gram-negative bacilli are particularly difficult to treat and highlight an urgent need for the development of new class of agents to combat these infections. In this work, a small library comprising thiourea and guanidine derivatives with low molecular weight was designed; these derivatives were studied as antimicrobial agents against Gram-positive, Gram-negative, and a panel of drug-resistant clinical isolates recovered from patients with CF. One novel compound, a guanidine derivative bearing adamantane-1-carbonyl and 2-bromo-4,6-difluouro-phenyl substituents (H-BDF), showed potent bactericidal activity against the strains tested, at levels generally higher than those exhibited by tobramycin, ceftazimide and meropenem. The role that different substituents exert in the antimicrobial activity has been determined, highlighting the importance of the halo-phenyl group in the guanidine moiety. The new compound displays low levels of cytotoxicity against THP-1 and A549 cells with a selective index (SI) > 8 (patent application PCT/IB2017/054870, August 2017). Taken together, our results indicate that H-BDF can be considered as a promising antimicrobial agent.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/87543
Saeed, Aamer; Bosch, María Alejandra; Bettiol, Marisa; Nossa González, Diana Lisseth; Erben, Mauricio Federico; et al.; Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species; Molecular Diversity Preservation International; Molecules; 23; 5; 5-2018; 1158-1170
1420-3049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87543
identifier_str_mv Saeed, Aamer; Bosch, María Alejandra; Bettiol, Marisa; Nossa González, Diana Lisseth; Erben, Mauricio Federico; et al.; Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species; Molecular Diversity Preservation International; Molecules; 23; 5; 5-2018; 1158-1170
1420-3049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23051158
info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/5/1158
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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