Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors

Autores
Malvacio, Ivana; Cuzzolin, Alberto; Sturlese, Mattia; Vera, Domingo Mariano Adolfo; Moyano, Elizabeth Laura; Moro, Stefano
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e 2 and 4h 2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.
Fil: Malvacio, Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Cuzzolin, Alberto. Università di Padova; Italia
Fil: Sturlese, Mattia. Università di Padova; Italia
Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Moyano, Elizabeth Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Moro, Stefano. Università di Padova; Italia
Materia
2-Aryl-2H-pyrazolo[4,3-c]qui- nolin-3-one
serine- threonine checkpoint kinase 1 (Chk1)
molecular docking
molecular dynamics
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:11336/43913
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitorsMalvacio, IvanaCuzzolin, AlbertoSturlese, MattiaVera, Domingo Mariano AdolfoMoyano, Elizabeth LauraMoro, Stefano2-Aryl-2H-pyrazolo[4,3-c]qui- nolin-3-oneserine- threonine checkpoint kinase 1 (Chk1)molecular dockingmolecular dynamicshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e 2 and 4h 2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.Fil: Malvacio, Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Cuzzolin, Alberto. Università di Padova; ItaliaFil: Sturlese, Mattia. Università di Padova; ItaliaFil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Moyano, Elizabeth Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Moro, Stefano. Università di Padova; ItaliaTaylor & Francis Ltd2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43913Malvacio, Ivana; Cuzzolin, Alberto; Sturlese, Mattia; Vera, Domingo Mariano Adolfo; Moyano, Elizabeth Laura; et al.; Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 33; 1; 12-2017; 171-1831475-6366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2017.1404592info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/14756366.2017.1404592info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:01Zoai:ri.conicet.gov.ar:11336/43913instacron: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:34982025-09-03 10:05:01.564CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
title Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
spellingShingle Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
Malvacio, Ivana
2-Aryl-2H-pyrazolo[4,3-c]qui- nolin-3-one
serine- threonine checkpoint kinase 1 (Chk1)
molecular docking
molecular dynamics
title_short Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
title_full Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
title_fullStr Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
title_full_unstemmed Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
title_sort Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
dc.creator.none.fl_str_mv Malvacio, Ivana
Cuzzolin, Alberto
Sturlese, Mattia
Vera, Domingo Mariano Adolfo
Moyano, Elizabeth Laura
Moro, Stefano
author Malvacio, Ivana
author_facet Malvacio, Ivana
Cuzzolin, Alberto
Sturlese, Mattia
Vera, Domingo Mariano Adolfo
Moyano, Elizabeth Laura
Moro, Stefano
author_role author
author2 Cuzzolin, Alberto
Sturlese, Mattia
Vera, Domingo Mariano Adolfo
Moyano, Elizabeth Laura
Moro, Stefano
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 2-Aryl-2H-pyrazolo[4,3-c]qui- nolin-3-one
serine- threonine checkpoint kinase 1 (Chk1)
molecular docking
molecular dynamics
topic 2-Aryl-2H-pyrazolo[4,3-c]qui- nolin-3-one
serine- threonine checkpoint kinase 1 (Chk1)
molecular docking
molecular dynamics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e 2 and 4h 2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.
Fil: Malvacio, Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Cuzzolin, Alberto. Università di Padova; Italia
Fil: Sturlese, Mattia. Università di Padova; Italia
Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina
Fil: Moyano, Elizabeth Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Moro, Stefano. Università di Padova; Italia
description The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e 2 and 4h 2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
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/11336/43913
Malvacio, Ivana; Cuzzolin, Alberto; Sturlese, Mattia; Vera, Domingo Mariano Adolfo; Moyano, Elizabeth Laura; et al.; Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 33; 1; 12-2017; 171-183
1475-6366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/43913
identifier_str_mv Malvacio, Ivana; Cuzzolin, Alberto; Sturlese, Mattia; Vera, Domingo Mariano Adolfo; Moyano, Elizabeth Laura; et al.; Synthesis and preliminary structure-activity relationship study of 2-aryl-2 H -pyrazolo[4,3- c ]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 33; 1; 12-2017; 171-183
1475-6366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2017.1404592
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/14756366.2017.1404592
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 Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
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 13.13397

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