Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
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. |
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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 |