Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units

Autores
Rodríguez, Diego F.; Durán Osorio, Francisca; Duarte, Yorley; Olivares, Pedro; Moglie, Yanina Fernanda; kamal, Dua; Zacconi, Flavia Cristina Milagro
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.
Fil: Rodríguez, Diego F.. Pontificia Universidad Católica de Chile; Chile
Fil: Durán Osorio, Francisca. Pontificia Universidad Católica de Chile; Chile
Fil: Duarte, Yorley. Universidad Andrés Bello; Chile
Fil: Olivares, Pedro. Universidad Andrés Bello; Chile
Fil: Moglie, Yanina Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: kamal, Dua. University of Sydney; Australia
Fil: Zacconi, Flavia Cristina Milagro. Pontificia Universidad Católica de Chile; Chile. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
CLICK CHEMISTRY
DOACS
DRUG DISCOVERY
FXA INHIBITORS
GREEN CHEMISTRY
MICROWAVE SYNTHESIS
ULLMANN-GOLDBERG REACTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/169673
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking unitsRodríguez, Diego F.Durán Osorio, FranciscaDuarte, YorleyOlivares, PedroMoglie, Yanina Fernandakamal, DuaZacconi, Flavia Cristina MilagroCLICK CHEMISTRYDOACSDRUG DISCOVERYFXA INHIBITORSGREEN CHEMISTRYMICROWAVE SYNTHESISULLMANN-GOLDBERG REACTIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.Fil: Rodríguez, Diego F.. Pontificia Universidad Católica de Chile; ChileFil: Durán Osorio, Francisca. Pontificia Universidad Católica de Chile; ChileFil: Duarte, Yorley. Universidad Andrés Bello; ChileFil: Olivares, Pedro. Universidad Andrés Bello; ChileFil: Moglie, Yanina Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: kamal, Dua. University of Sydney; AustraliaFil: Zacconi, Flavia Cristina Milagro. Pontificia Universidad Católica de Chile; Chile. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169673Rodríguez, Diego F.; Durán Osorio, Francisca; Duarte, Yorley; Olivares, Pedro; Moglie, Yanina Fernanda; et al.; Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units; MDPI; Pharmaceutics; 14; 1; 12-2021; 1-151999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/14/1/33info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics14010033info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:38Zoai:ri.conicet.gov.ar:11336/169673instacron: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 09:44:38.672CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
title Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
spellingShingle Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
Rodríguez, Diego F.
CLICK CHEMISTRY
DOACS
DRUG DISCOVERY
FXA INHIBITORS
GREEN CHEMISTRY
MICROWAVE SYNTHESIS
ULLMANN-GOLDBERG REACTION
title_short Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
title_full Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
title_fullStr Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
title_full_unstemmed Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
title_sort Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units
dc.creator.none.fl_str_mv Rodríguez, Diego F.
Durán Osorio, Francisca
Duarte, Yorley
Olivares, Pedro
Moglie, Yanina Fernanda
kamal, Dua
Zacconi, Flavia Cristina Milagro
author Rodríguez, Diego F.
author_facet Rodríguez, Diego F.
Durán Osorio, Francisca
Duarte, Yorley
Olivares, Pedro
Moglie, Yanina Fernanda
kamal, Dua
Zacconi, Flavia Cristina Milagro
author_role author
author2 Durán Osorio, Francisca
Duarte, Yorley
Olivares, Pedro
Moglie, Yanina Fernanda
kamal, Dua
Zacconi, Flavia Cristina Milagro
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CLICK CHEMISTRY
DOACS
DRUG DISCOVERY
FXA INHIBITORS
GREEN CHEMISTRY
MICROWAVE SYNTHESIS
ULLMANN-GOLDBERG REACTION
topic CLICK CHEMISTRY
DOACS
DRUG DISCOVERY
FXA INHIBITORS
GREEN CHEMISTRY
MICROWAVE SYNTHESIS
ULLMANN-GOLDBERG REACTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.
Fil: Rodríguez, Diego F.. Pontificia Universidad Católica de Chile; Chile
Fil: Durán Osorio, Francisca. Pontificia Universidad Católica de Chile; Chile
Fil: Duarte, Yorley. Universidad Andrés Bello; Chile
Fil: Olivares, Pedro. Universidad Andrés Bello; Chile
Fil: Moglie, Yanina Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: kamal, Dua. University of Sydney; Australia
Fil: Zacconi, Flavia Cristina Milagro. Pontificia Universidad Católica de Chile; Chile. Pontificia Universidad Catolica de Chile. Facultad de Ciencias Biológicas; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
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/11336/169673
Rodríguez, Diego F.; Durán Osorio, Francisca; Duarte, Yorley; Olivares, Pedro; Moglie, Yanina Fernanda; et al.; Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units; MDPI; Pharmaceutics; 14; 1; 12-2021; 1-15
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/169673
identifier_str_mv Rodríguez, Diego F.; Durán Osorio, Francisca; Duarte, Yorley; Olivares, Pedro; Moglie, Yanina Fernanda; et al.; Green by design: Convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units; MDPI; Pharmaceutics; 14; 1; 12-2021; 1-15
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/14/1/33
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics14010033
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/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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