Antiproliferative and quinone reductase-inducing activities of withanolides derivatives

Autores
García, Manuela Emila; Nicotra, Viviana Estela; Oberti, Juan Carlos María; Ríos Luci, Carla; Leon, Leticia G.; Marler, Laura; Li, Guannan; Pezzuto, John; Van Breemen, Richard B.; Padron, Jose; Hueso Falcon, Idaira; Estevez Braun, Ana
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structureeactivity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4b,12b,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-olide (18) and (23R)-21-acetoxy-12b-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-lactame (20).
Fil: García, Manuela Emila. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Nicotra, Viviana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina
Fil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina
Fil: Ríos Luci, Carla. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Leon, Leticia G.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Marler, Laura. University of Hawaii at Hilo. The Daniel K. Inouye College of Pharmacy; Estados Unidos
Fil: Li, Guannan. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados Unidos
Fil: Pezzuto, John. College Of Pharmacy, University Of Hawaii At Hilo;
Fil: Van Breemen, Richard B.. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados Unidos
Fil: Padron, Jose. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Hueso Falcon, Idaira. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Estevez Braun, Ana. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Materia
Withanolide Derivatives
Jaborosa Runcinata
Antiproliferative Activity
Quinone-Reductase Induction
Keap1 Protein
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18078
Acceder
id CONICETDig_ad987df79d656e9cdfa6e572fb851b53
oai_identifier_str oai:ri.conicet.gov.ar:11336/18078
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiproliferative and quinone reductase-inducing activities of withanolides derivativesGarcía, Manuela EmilaNicotra, Viviana EstelaOberti, Juan Carlos MaríaRíos Luci, CarlaLeon, Leticia G.Marler, LauraLi, GuannanPezzuto, JohnVan Breemen, Richard B.Padron, JoseHueso Falcon, IdairaEstevez Braun, AnaWithanolide DerivativesJaborosa RuncinataAntiproliferative ActivityQuinone-Reductase InductionKeap1 Proteinhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structureeactivity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4b,12b,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-olide (18) and (23R)-21-acetoxy-12b-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-lactame (20).Fil: García, Manuela Emila. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Nicotra, Viviana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; ArgentinaFil: Ríos Luci, Carla. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; EspañaFil: Leon, Leticia G.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; EspañaFil: Marler, Laura. University of Hawaii at Hilo. The Daniel K. Inouye College of Pharmacy; Estados UnidosFil: Li, Guannan. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados UnidosFil: Pezzuto, John. College Of Pharmacy, University Of Hawaii At Hilo;Fil: Van Breemen, Richard B.. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados UnidosFil: Padron, Jose. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; EspañaFil: Hueso Falcon, Idaira. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; EspañaFil: Estevez Braun, Ana. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; EspañaElsevier Masson2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18078García, Manuela Emila; Nicotra, Viviana Estela; Oberti, Juan Carlos María; Ríos Luci, Carla; Leon, Leticia G.; et al.; Antiproliferative and quinone reductase-inducing activities of withanolides derivatives; Elsevier Masson; European Journal Of Medical Chemistry; 82; 5-2014; 68-810223-52341768-3254enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523414004693info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2014.05.045info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:03Zoai:ri.conicet.gov.ar:11336/18078instacron: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 09:51:04.14CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
title Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
spellingShingle Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
García, Manuela Emila
Withanolide Derivatives
Jaborosa Runcinata
Antiproliferative Activity
Quinone-Reductase Induction
Keap1 Protein
title_short Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
title_full Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
title_fullStr Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
title_full_unstemmed Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
title_sort Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
dc.creator.none.fl_str_mv García, Manuela Emila
Nicotra, Viviana Estela
Oberti, Juan Carlos María
Ríos Luci, Carla
Leon, Leticia G.
Marler, Laura
Li, Guannan
Pezzuto, John
Van Breemen, Richard B.
Padron, Jose
Hueso Falcon, Idaira
Estevez Braun, Ana
author García, Manuela Emila
author_facet García, Manuela Emila
Nicotra, Viviana Estela
Oberti, Juan Carlos María
Ríos Luci, Carla
Leon, Leticia G.
Marler, Laura
Li, Guannan
Pezzuto, John
Van Breemen, Richard B.
Padron, Jose
Hueso Falcon, Idaira
Estevez Braun, Ana
author_role author
author2 Nicotra, Viviana Estela
Oberti, Juan Carlos María
Ríos Luci, Carla
Leon, Leticia G.
Marler, Laura
Li, Guannan
Pezzuto, John
Van Breemen, Richard B.
Padron, Jose
Hueso Falcon, Idaira
Estevez Braun, Ana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Withanolide Derivatives
Jaborosa Runcinata
Antiproliferative Activity
Quinone-Reductase Induction
Keap1 Protein
topic Withanolide Derivatives
Jaborosa Runcinata
Antiproliferative Activity
Quinone-Reductase Induction
Keap1 Protein
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structureeactivity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4b,12b,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-olide (18) and (23R)-21-acetoxy-12b-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-lactame (20).
Fil: García, Manuela Emila. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Nicotra, Viviana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina
Fil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina
Fil: Ríos Luci, Carla. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Leon, Leticia G.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Marler, Laura. University of Hawaii at Hilo. The Daniel K. Inouye College of Pharmacy; Estados Unidos
Fil: Li, Guannan. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados Unidos
Fil: Pezzuto, John. College Of Pharmacy, University Of Hawaii At Hilo;
Fil: Van Breemen, Richard B.. University of Illinois at Chicago. College of Pharmacy. Department of Medicinal Chemistry and Pharmacognosy; Estados Unidos
Fil: Padron, Jose. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Hueso Falcon, Idaira. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
Fil: Estevez Braun, Ana. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "antonio Gonzalez"; España
description Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structureeactivity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4b,12b,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-olide (18) and (23R)-21-acetoxy-12b-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen- 26,23-lactame (20).
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/18078
García, Manuela Emila; Nicotra, Viviana Estela; Oberti, Juan Carlos María; Ríos Luci, Carla; Leon, Leticia G.; et al.; Antiproliferative and quinone reductase-inducing activities of withanolides derivatives; Elsevier Masson; European Journal Of Medical Chemistry; 82; 5-2014; 68-81
0223-5234
1768-3254
url http://hdl.handle.net/11336/18078
identifier_str_mv García, Manuela Emila; Nicotra, Viviana Estela; Oberti, Juan Carlos María; Ríos Luci, Carla; Leon, Leticia G.; et al.; Antiproliferative and quinone reductase-inducing activities of withanolides derivatives; Elsevier Masson; European Journal Of Medical Chemistry; 82; 5-2014; 68-81
0223-5234
1768-3254
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523414004693
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2014.05.045
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
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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