A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents

An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of car...

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Autores: Del Corte Solaguren-Beascoa, Xabier, López Francés, Adrián, Maestro Burzaco, Aitor, Villate Beitia, Ane Ilia, Sainz Ramos, Myriam, Martínez de Marigorta Izaga, Edorta, Pedraz Muñoz, José Luis, Palacios Gambra, Francisco Javier, Vicario Hernando, Javier
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/53075
Acceso en línea:http://hdl.handle.net/10810/53075
Access Level:acceso abierto
Palabra clave:γ-lactams
multicomponent synthesis
antiproliferative effect
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spelling A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative AgentsDel Corte Solaguren-Beascoa, XabierLópez Francés, AdriánMaestro Burzaco, AitorVillate Beitia, Ane IliaSainz Ramos, MyriamMartínez de Marigorta Izaga, EdortaPedraz Muñoz, José LuisPalacios Gambra, Francisco JavierVicario Hernando, Javierγ-lactamsmulticomponent synthesisantiproliferative effectAn efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.Financial support by Ministerio de Economía, Industria y Competividad (MINECO) (RTI2018-101818-B-I00) and Gobierno Vasco (GV, IT 992-16) is gratefully acknowledged. The authors thank SGIker (UPV/EHU/ERDF, EU) for the technical and human support provided. X.d.C. and A.L.-F. thank the Basque Country Government for a predoctoral grant. I.V.-B. thanks the University of the Basque Country (UPV/EHU) for the granted postdoctoral fellowship (ESPDOC19/47). M.S.-R. thanks the University of the Basque Country (UPV/EHU) for the granted pre-doctoral fellowship (PIF17/79).MDPI2021202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/53075reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/RTI2018-101818-B-I00/https://www.mdpi.com/1424-8247/14/8/782/htminfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).oai:addi.ehu.eus:10810/530752026-06-18T09:23:17Z
dc.title.none.fl_str_mv A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
title A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
spellingShingle A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
Del Corte Solaguren-Beascoa, Xabier
γ-lactams
multicomponent synthesis
antiproliferative effect
title_short A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
title_full A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
title_fullStr A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
title_full_unstemmed A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
title_sort A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents
dc.creator.none.fl_str_mv Del Corte Solaguren-Beascoa, Xabier
López Francés, Adrián
Maestro Burzaco, Aitor
Villate Beitia, Ane Ilia
Sainz Ramos, Myriam
Martínez de Marigorta Izaga, Edorta
Pedraz Muñoz, José Luis
Palacios Gambra, Francisco Javier
Vicario Hernando, Javier
author Del Corte Solaguren-Beascoa, Xabier
author_facet Del Corte Solaguren-Beascoa, Xabier
López Francés, Adrián
Maestro Burzaco, Aitor
Villate Beitia, Ane Ilia
Sainz Ramos, Myriam
Martínez de Marigorta Izaga, Edorta
Pedraz Muñoz, José Luis
Palacios Gambra, Francisco Javier
Vicario Hernando, Javier
author_role author
author2 López Francés, Adrián
Maestro Burzaco, Aitor
Villate Beitia, Ane Ilia
Sainz Ramos, Myriam
Martínez de Marigorta Izaga, Edorta
Pedraz Muñoz, José Luis
Palacios Gambra, Francisco Javier
Vicario Hernando, Javier
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv γ-lactams
multicomponent synthesis
antiproliferative effect
topic γ-lactams
multicomponent synthesis
antiproliferative effect
description An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/53075
url http://hdl.handle.net/10810/53075
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/RTI2018-101818-B-I00/
https://www.mdpi.com/1424-8247/14/8/782/htm
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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