Multicomponent Synthesis of Unsaturated γ-Lactam Derivatives. Applications as Antiproliferative Agents through the Bioisosterism Approach: Carbonyl vs. Phosphoryl Group
dc.contributor.author | Del Corte Solaguren-Beascoa, Xabier | |
dc.contributor.author | López Francés, Adrián | |
dc.contributor.author | Villate Beitia, Ane Ilia | |
dc.contributor.author | Sainz Ramos, Myriam | |
dc.contributor.author | Martínez de Marigorta Izaga, Edorta | |
dc.contributor.author | Palacios Gambra, Francisco Javier | |
dc.contributor.author | Alonso Pérez, Concepción Estibaliz | |
dc.contributor.author | De los Santos Ruiz, Jesús Manuel | |
dc.contributor.author | Pedraz Muñoz, José Luis | |
dc.contributor.author | Vicario Hernando, Javier | |
dc.date.accessioned | 2022-05-31T08:40:43Z | |
dc.date.available | 2022-05-31T08:40:43Z | |
dc.date.issued | 2022-04-22 | |
dc.identifier.citation | Pharmaceuticals 15(5) : (2022) // Article ID 511 | es_ES |
dc.identifier.issn | 1424-8247 | |
dc.identifier.uri | http://hdl.handle.net/10810/56801 | |
dc.description.abstract | We report efficient synthetic methodologies for the preparation of 3-amino and 3-hydroxy 3-pyrrolin-2-ones (unsaturated γ-lactams) through a multicomponent reaction of amines, aldehydes and acetylene or pyruvate derivatives. The densely substituted γ-lactam substrates show in vitro cytotoxicity, inhibiting the growth of the carcinoma human tumor cell lines RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma) and A549 (carcinomic human alveolar basal epithelial cell). In view of the possibilities for the diversity of the substituents that offer a multicomponent, synthetic methodology, an extensive structure–activity profile is presented. In addition, the bioisosteric replacement of the flat ester group by a tetrahedral phosphonate or phosphine oxide moiety in γ-lactam substrates leads to increased growth inhibition activity. 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. | es_ES |
dc.description.sponsorship | Financial support by Ministerio de Economía, Industria y Competividad (MINECO) (RTI2018-101818-B-I00) and Gobierno Vasco (GV, IT 992-16) is gratefully acknowledged. 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 a postdoctoral fellowship (ESPDOC19/47). M.S.-R. thanks the University of the Basque Country (UPV/EHU) for a pre-doctoral fellowship (PIF17/79). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RTI2018-101818-B-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | γ-lactams | es_ES |
dc.subject | multicomponent synthesis | es_ES |
dc.subject | antiproliferative activity | es_ES |
dc.subject | bioisosterism | es_ES |
dc.subject | phosphonates | es_ES |
dc.subject | phosphine oxides | es_ES |
dc.title | Multicomponent Synthesis of Unsaturated γ-Lactam Derivatives. Applications as Antiproliferative Agents through the Bioisosterism Approach: Carbonyl vs. Phosphoryl Group | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2022-05-27T13:37:05Z | |
dc.rights.holder | 2022 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/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1424-8247/15/5/511/htm | es_ES |
dc.identifier.doi | 10.3390/ph15050511 | |
dc.departamentoes | Química orgánica I | |
dc.departamentoeu | Kimika organikoa I |
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Except where otherwise noted, this item's license is described as 2022 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/).