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

Autores
Saeed, Aamer; Bosch, María Alejandra; Bettiol, Marisa; Nossa González, Diana L.; 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.
Centro de Química Inorgánica (CEQUINOR)
Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI)
Facultad de Ciencias Exactas
Materia
Química
antimicrobials
thioureas
guanidines
drug-resistant
cystic fibrosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/81365

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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial SpeciesSaeed, AamerBosch, María AlejandraBettiol, MarisaNossa González, Diana L.Erben, Mauricio FedericoLamberti, Yanina AndreaQuímicaantimicrobialsthioureasguanidinesdrug-resistantcystic fibrosisChronic 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.Centro de Química Inorgánica (CEQUINOR)Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI)Facultad de Ciencias Exactas2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/81365enginfo:eu-repo/semantics/altIdentifier/issn/1420-3049info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23051158info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:15:07Zoai:sedici.unlp.edu.ar:10915/81365Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:15:07.627SEDICI (UNLP) - Universidad Nacional de La Platafalse
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
Química
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 L.
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author Saeed, Aamer
author_facet Saeed, Aamer
Bosch, María Alejandra
Bettiol, Marisa
Nossa González, Diana L.
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author_role author
author2 Bosch, María Alejandra
Bettiol, Marisa
Nossa González, Diana L.
Erben, Mauricio Federico
Lamberti, Yanina Andrea
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Química
antimicrobials
thioureas
guanidines
drug-resistant
cystic fibrosis
topic Química
antimicrobials
thioureas
guanidines
drug-resistant
cystic fibrosis
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.
Centro de Química Inorgánica (CEQUINOR)
Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI)
Facultad de Ciencias Exactas
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
Articulo
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://sedici.unlp.edu.ar/handle/10915/81365
url http://sedici.unlp.edu.ar/handle/10915/81365
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1420-3049
info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23051158
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
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reponame_str SEDICI (UNLP)
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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