Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
dc.contributor.author | Selas Lanseros, Asier | |
dc.contributor.author | Fuertes Sánchez, María | |
dc.contributor.author | Melcón-Fernández, Estela | |
dc.contributor.author | Pérez-Pertejo, Yolanda | |
dc.contributor.author | Reguera, Rosa M. | |
dc.contributor.author | Balaña-Fouce, Rafael | |
dc.contributor.author | Knudsen, Birgitta Ruth | |
dc.contributor.author | Palacios Gambra, Francisco Javier | |
dc.contributor.author | Alonso Pérez, Concepción Estibaliz | |
dc.date.accessioned | 2021-09-13T10:16:32Z | |
dc.date.available | 2021-09-13T10:16:32Z | |
dc.date.issued | 2021-08-09 | |
dc.identifier.citation | Pharmaceuticals 14(8) : (2021) // Article ID 784 | es_ES |
dc.identifier.issn | 1424-8247 | |
dc.identifier.uri | http://hdl.handle.net/10810/53076 | |
dc.description.abstract | This work describes, for the first time, the synthesis of dialkyl (2-arylquinolin-8-yl)phosphonate derivatives. The preparation was carried out through a direct and simple process as a multicomponent Povarov reaction of aminophenylphosphonates, aldehydes, and styrenes and subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or, alternatively, by a cycloaddition reaction between phosphonate aldimines and acetylenes. Based on phosphonate group structural characteristics, considered as phosphorous isosteres of carboxylic heterocycles, they may present interesting biological properties related to cell proliferation. In the current report, a new series of dialkyl (2-arylquinolin-8-yl)phosphonates have been synthesized and their antiproliferative effect evaluated on different human cancer and embryonic cells, as well as on Leishmania infantum parasites, a eukaryotic protist responsible for visceral leishmaniasis. Thereby, the antitumor effect was assessed in human lung adenocarcinoma cells (A549), human ovarian carcinoma cells (SKOV3), and human embryonic kidney cells (HEK293) versus the non-cancerous lung fibroblasts cell line (MRC5). On the other hand, the antileishmanial activity was tested against both stages of L. infantum cell cycle, namely free-living promastigotes and intramacrophage amastigotes, using a primary culture of Balb/c splenocytes to calculate the selectivity index. Besides the antiproliferative and antileishmanial capacities, their behavior as topoisomerase 1B inhibitors has been evaluated as a possible mechanism of action. | es_ES |
dc.description.sponsorship | This research was financially supported by Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) y Fondo Europeo de Desarrollo Regional (FEDER; RTI2018–101818-B-I00, UE) and by Gobierno Vasco, Universidad del País Vasco (GV, IT 992–16; UPV) is gratefully acknowledged. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF, and ESF) is gratefully acknowledged. AS thanks the Basque Government for a formation contract. This collaborative research was funded by MINECO; SAF2017–83575-R to RMR. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017–83575-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | quinolinyl phosphonates | es_ES |
dc.subject | topoisomerase 1B | es_ES |
dc.subject | enzyme inhibition | es_ES |
dc.subject | antiproliferative effect | es_ES |
dc.subject | leishmaniosis effect | es_ES |
dc.title | Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B) | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-09-09T13:44:55Z | |
dc.rights.holder | 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/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1424-8247/14/8/784/htm | es_ES |
dc.identifier.doi | 10.3390/ph14080784 | |
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 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/).