Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump

Detalhes bibliográficos
Autor(a) principal: Dantas, Natalina
Data de Publicação: 2018
Outros Autores: de Aquino, Thiago Mendonça, de Araújo-Júnior, João Xavier, da Silva-Júnior, Edeildo, Gomes, Ednaldo Almeida, Gomes, Antoniel Augusto Severo [UNESP], Siqueira-Júnior, José Pinto, Mendonça Junior, Francisco Jaime Bezerra
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.cbi.2017.12.009
http://hdl.handle.net/11449/170454
Resumo: One of the promising fields for improving the effectiveness of antimicrobial agents is their combination with efflux pump inhibitors (EPIs), which besides expanding the use of existing antibiotics. The goal of this research was to evaluate a series of aminoguanidine hydrazones (AGH's, 1–19) as antibacterial agents and NorA efflux pump inhibitors in Staphylococcus aureus strain SA-1199B. Molecular modeling and docking studies were also performed in order to explain at the molecular level the interactions of the compounds with the generated NorA efflux pump model. The MICs of the antibiotic and ethidium bromide were determined by microdilution assay in absence or presence of a subinhibitory concentration of aminoguanidine hydrazones and macrophages viability was determined through MTT assay. Bioinformatic software Swiss-Model and AutoDock 4.2 were used to perform modeling and docking studies, respectively. As results, all AGH's were able to potentiate the action for the antibiotic norfloxacin, causing MIC's reduction of 16-fold and 32-fold to ethidium bromide. In the cell viability test, the concentration of 10 μg/mL showed better results than 90% and the concentration of 1000 μg/mL showed the lowest viability, reaching a maximum of 50% for the analyzed aminoguanidine hydrazones. Molecular docking studies showed that both norfloxacin and derivative 13 were recognized by the same binding site of NorA pump, suggesting a competitive mechanism. The present work demonstrated for the first time that AGH derivatives have potential to be putative inhibitors of NorA efflux pump, showing a promising activity as an antibacterial drug development.
id UNSP_d83ba4f8813b556cfe7cd8784b958ba5
oai_identifier_str oai:repositorio.unesp.br:11449/170454
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pumpAminoguanidine hydrazonesDockingEfflux pump inhibitorsStaphylococcus aureusOne of the promising fields for improving the effectiveness of antimicrobial agents is their combination with efflux pump inhibitors (EPIs), which besides expanding the use of existing antibiotics. The goal of this research was to evaluate a series of aminoguanidine hydrazones (AGH's, 1–19) as antibacterial agents and NorA efflux pump inhibitors in Staphylococcus aureus strain SA-1199B. Molecular modeling and docking studies were also performed in order to explain at the molecular level the interactions of the compounds with the generated NorA efflux pump model. The MICs of the antibiotic and ethidium bromide were determined by microdilution assay in absence or presence of a subinhibitory concentration of aminoguanidine hydrazones and macrophages viability was determined through MTT assay. Bioinformatic software Swiss-Model and AutoDock 4.2 were used to perform modeling and docking studies, respectively. As results, all AGH's were able to potentiate the action for the antibiotic norfloxacin, causing MIC's reduction of 16-fold and 32-fold to ethidium bromide. In the cell viability test, the concentration of 10 μg/mL showed better results than 90% and the concentration of 1000 μg/mL showed the lowest viability, reaching a maximum of 50% for the analyzed aminoguanidine hydrazones. Molecular docking studies showed that both norfloxacin and derivative 13 were recognized by the same binding site of NorA pump, suggesting a competitive mechanism. The present work demonstrated for the first time that AGH derivatives have potential to be putative inhibitors of NorA efflux pump, showing a promising activity as an antibacterial drug development.Laboratório de Genética de Microorganismo Departamento de Biologia Molecular/CCEN/Universidade Federal da Paraíba-UFPBLaboratório de Química Medicinal Escola de Enfermagem e Farmácia Universidade Federal de Alagoas/UFALDepartamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista UNESPLaboratório de Síntese e Planejamento de Fármacos Departamento de Ciências Biológicas/CCBSA Universidade Estadual da Paraíba-UEPBDepartamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista UNESPUniversidade Federal da Paraíba (UFPB)Universidade Federal de Alagoas/UFALUniversidade Estadual Paulista (Unesp)Universidade Estadual da Paraíba-UEPBDantas, Natalinade Aquino, Thiago Mendonçade Araújo-Júnior, João Xavierda Silva-Júnior, EdeildoGomes, Ednaldo AlmeidaGomes, Antoniel Augusto Severo [UNESP]Siqueira-Júnior, José PintoMendonça Junior, Francisco Jaime Bezerra2018-12-11T16:50:52Z2018-12-11T16:50:52Z2018-01-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8-14application/pdfhttp://dx.doi.org/10.1016/j.cbi.2017.12.009Chemico-Biological Interactions, v. 280, p. 8-14.1872-77860009-2797http://hdl.handle.net/11449/17045410.1016/j.cbi.2017.12.0092-s2.0-850376645132-s2.0-85037664513.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengChemico-Biological Interactions1,033info:eu-repo/semantics/openAccess2023-12-07T06:18:14Zoai:repositorio.unesp.br:11449/170454Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:42:50.490282Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
title Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
spellingShingle Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
Dantas, Natalina
Aminoguanidine hydrazones
Docking
Efflux pump inhibitors
Staphylococcus aureus
title_short Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
title_full Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
title_fullStr Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
title_full_unstemmed Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
title_sort Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
author Dantas, Natalina
author_facet Dantas, Natalina
de Aquino, Thiago Mendonça
de Araújo-Júnior, João Xavier
da Silva-Júnior, Edeildo
Gomes, Ednaldo Almeida
Gomes, Antoniel Augusto Severo [UNESP]
Siqueira-Júnior, José Pinto
Mendonça Junior, Francisco Jaime Bezerra
author_role author
author2 de Aquino, Thiago Mendonça
de Araújo-Júnior, João Xavier
da Silva-Júnior, Edeildo
Gomes, Ednaldo Almeida
Gomes, Antoniel Augusto Severo [UNESP]
Siqueira-Júnior, José Pinto
Mendonça Junior, Francisco Jaime Bezerra
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal da Paraíba (UFPB)
Universidade Federal de Alagoas/UFAL
Universidade Estadual Paulista (Unesp)
Universidade Estadual da Paraíba-UEPB
dc.contributor.author.fl_str_mv Dantas, Natalina
de Aquino, Thiago Mendonça
de Araújo-Júnior, João Xavier
da Silva-Júnior, Edeildo
Gomes, Ednaldo Almeida
Gomes, Antoniel Augusto Severo [UNESP]
Siqueira-Júnior, José Pinto
Mendonça Junior, Francisco Jaime Bezerra
dc.subject.por.fl_str_mv Aminoguanidine hydrazones
Docking
Efflux pump inhibitors
Staphylococcus aureus
topic Aminoguanidine hydrazones
Docking
Efflux pump inhibitors
Staphylococcus aureus
description One of the promising fields for improving the effectiveness of antimicrobial agents is their combination with efflux pump inhibitors (EPIs), which besides expanding the use of existing antibiotics. The goal of this research was to evaluate a series of aminoguanidine hydrazones (AGH's, 1–19) as antibacterial agents and NorA efflux pump inhibitors in Staphylococcus aureus strain SA-1199B. Molecular modeling and docking studies were also performed in order to explain at the molecular level the interactions of the compounds with the generated NorA efflux pump model. The MICs of the antibiotic and ethidium bromide were determined by microdilution assay in absence or presence of a subinhibitory concentration of aminoguanidine hydrazones and macrophages viability was determined through MTT assay. Bioinformatic software Swiss-Model and AutoDock 4.2 were used to perform modeling and docking studies, respectively. As results, all AGH's were able to potentiate the action for the antibiotic norfloxacin, causing MIC's reduction of 16-fold and 32-fold to ethidium bromide. In the cell viability test, the concentration of 10 μg/mL showed better results than 90% and the concentration of 1000 μg/mL showed the lowest viability, reaching a maximum of 50% for the analyzed aminoguanidine hydrazones. Molecular docking studies showed that both norfloxacin and derivative 13 were recognized by the same binding site of NorA pump, suggesting a competitive mechanism. The present work demonstrated for the first time that AGH derivatives have potential to be putative inhibitors of NorA efflux pump, showing a promising activity as an antibacterial drug development.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-11T16:50:52Z
2018-12-11T16:50:52Z
2018-01-25
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.cbi.2017.12.009
Chemico-Biological Interactions, v. 280, p. 8-14.
1872-7786
0009-2797
http://hdl.handle.net/11449/170454
10.1016/j.cbi.2017.12.009
2-s2.0-85037664513
2-s2.0-85037664513.pdf
url http://dx.doi.org/10.1016/j.cbi.2017.12.009
http://hdl.handle.net/11449/170454
identifier_str_mv Chemico-Biological Interactions, v. 280, p. 8-14.
1872-7786
0009-2797
10.1016/j.cbi.2017.12.009
2-s2.0-85037664513
2-s2.0-85037664513.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Chemico-Biological Interactions
1,033
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8-14
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808129108700299264