Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs

Autores
Funes Chabán, Macarena; Hrast, M.; Frlan, R.; Graikioti, D. G.; Athanassopoulos, Constantinos M.; Carpinella, Maria Cecilia
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validatedas targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenesand synthetic analogs derived therefrom were investigated for their inhibitory properties on theseenzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effectivefor inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 M. To furthermechanistically investigate the nature of binding and to explain the activity, these compounds weredocked into the active site of MurA from E. coli. The aromatic ring of the active compounds showeda T-shaped ? interaction with the phenyl ring of Phe328, and at least one hydrogen bond wasformed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establishnew chemical scaffolds for the development of novel entities targeting MurA as potential antibioticsto combat the threat of pathogenic bacteria, particularly resistant strains.
Fil: Funes Chabán, Macarena. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Hrast, M.. University Of Ljubljana. Faculty Of Pharmacy; Eslovenia
Fil: Frlan, R.. University Of Ljubljana. Faculty Of Pharmacy; Eslovenia
Fil: Graikioti, D. G.. University Of Patras. Department Of Chemistry; Grecia
Fil: Athanassopoulos, Constantinos M.. University Of Patras. Department Of Chemistry; Grecia
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Materia
INHIBIDORES DE ENZIMAS MUR
ANTIBACTERIANOS
DITERPENOS
DERIVADOS SINTETICOS
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:11336/182784
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/182784
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogsFunes Chabán, MacarenaHrast, M.Frlan, R.Graikioti, D. G.Athanassopoulos, Constantinos M.Carpinella, Maria CeciliaINHIBIDORES DE ENZIMAS MURANTIBACTERIANOSDITERPENOSDERIVADOS SINTETICOShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validatedas targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenesand synthetic analogs derived therefrom were investigated for their inhibitory properties on theseenzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effectivefor inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 M. To furthermechanistically investigate the nature of binding and to explain the activity, these compounds weredocked into the active site of MurA from E. coli. The aromatic ring of the active compounds showeda T-shaped ? interaction with the phenyl ring of Phe328, and at least one hydrogen bond wasformed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establishnew chemical scaffolds for the development of novel entities targeting MurA as potential antibioticsto combat the threat of pathogenic bacteria, particularly resistant strains.Fil: Funes Chabán, Macarena. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Hrast, M.. University Of Ljubljana. Faculty Of Pharmacy; EsloveniaFil: Frlan, R.. University Of Ljubljana. Faculty Of Pharmacy; EsloveniaFil: Graikioti, D. G.. University Of Patras. Department Of Chemistry; GreciaFil: Athanassopoulos, Constantinos M.. University Of Patras. Department Of Chemistry; GreciaFil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaMDPI2021-12-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182784Funes Chabán, Macarena; Hrast, M.; Frlan, R.; Graikioti, D. G.; Athanassopoulos, Constantinos M.; et al.; Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs; MDPI; Antibiotics; 10; 12; 15-12-2021; 1-152079-6382CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/antibiotics10121535info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2079-6382/10/12/1535info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:45Zoai:ri.conicet.gov.ar:11336/182784instacron: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 10:23:46.244CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
title Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
spellingShingle Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
Funes Chabán, Macarena
INHIBIDORES DE ENZIMAS MUR
ANTIBACTERIANOS
DITERPENOS
DERIVADOS SINTETICOS
title_short Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
title_full Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
title_fullStr Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
title_full_unstemmed Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
title_sort Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs
dc.creator.none.fl_str_mv Funes Chabán, Macarena
Hrast, M.
Frlan, R.
Graikioti, D. G.
Athanassopoulos, Constantinos M.
Carpinella, Maria Cecilia
author Funes Chabán, Macarena
author_facet Funes Chabán, Macarena
Hrast, M.
Frlan, R.
Graikioti, D. G.
Athanassopoulos, Constantinos M.
Carpinella, Maria Cecilia
author_role author
author2 Hrast, M.
Frlan, R.
Graikioti, D. G.
Athanassopoulos, Constantinos M.
Carpinella, Maria Cecilia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv INHIBIDORES DE ENZIMAS MUR
ANTIBACTERIANOS
DITERPENOS
DERIVADOS SINTETICOS
topic INHIBIDORES DE ENZIMAS MUR
ANTIBACTERIANOS
DITERPENOS
DERIVADOS SINTETICOS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validatedas targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenesand synthetic analogs derived therefrom were investigated for their inhibitory properties on theseenzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effectivefor inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 M. To furthermechanistically investigate the nature of binding and to explain the activity, these compounds weredocked into the active site of MurA from E. coli. The aromatic ring of the active compounds showeda T-shaped ? interaction with the phenyl ring of Phe328, and at least one hydrogen bond wasformed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establishnew chemical scaffolds for the development of novel entities targeting MurA as potential antibioticsto combat the threat of pathogenic bacteria, particularly resistant strains.
Fil: Funes Chabán, Macarena. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
Fil: Hrast, M.. University Of Ljubljana. Faculty Of Pharmacy; Eslovenia
Fil: Frlan, R.. University Of Ljubljana. Faculty Of Pharmacy; Eslovenia
Fil: Graikioti, D. G.. University Of Patras. Department Of Chemistry; Grecia
Fil: Athanassopoulos, Constantinos M.. University Of Patras. Department Of Chemistry; Grecia
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina
description Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validatedas targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenesand synthetic analogs derived therefrom were investigated for their inhibitory properties on theseenzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effectivefor inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 M. To furthermechanistically investigate the nature of binding and to explain the activity, these compounds weredocked into the active site of MurA from E. coli. The aromatic ring of the active compounds showeda T-shaped ? interaction with the phenyl ring of Phe328, and at least one hydrogen bond wasformed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establishnew chemical scaffolds for the development of novel entities targeting MurA as potential antibioticsto combat the threat of pathogenic bacteria, particularly resistant strains.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-15
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/11336/182784
Funes Chabán, Macarena; Hrast, M.; Frlan, R.; Graikioti, D. G.; Athanassopoulos, Constantinos M.; et al.; Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs; MDPI; Antibiotics; 10; 12; 15-12-2021; 1-15
2079-6382
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182784
identifier_str_mv Funes Chabán, Macarena; Hrast, M.; Frlan, R.; Graikioti, D. G.; Athanassopoulos, Constantinos M.; et al.; Inhibition of MurA enzyme from Escherichia coli and Staphy-lococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs; MDPI; Antibiotics; 10; 12; 15-12-2021; 1-15
2079-6382
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/antibiotics10121535
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2079-6382/10/12/1535
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
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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