Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)

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...

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Autores: Selas Lanseros, Asier, Fuertes Sánchez, María, Melcón-Fernández, Estela, Pérez-Pertejo, Yolanda, Reguera, Rosa M., Balaña-Fouce, Rafael, Knudsen, Birgitta Ruth, Palacios Gambra, Francisco Javier, Alonso Pérez, Concepción Estibaliz
Tipo de documento: artigo
Data de publicação:2021
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/53076
Acesso em linha:http://hdl.handle.net/10810/53076
Access Level:Acceso aberto
Palavra-chave:quinolinyl phosphonates
topoisomerase 1B
enzyme inhibition
antiproliferative effect
leishmaniosis effect
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spelling Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)Selas Lanseros, AsierFuertes Sánchez, MaríaMelcón-Fernández, EstelaPérez-Pertejo, YolandaReguera, Rosa M.Balaña-Fouce, RafaelKnudsen, Birgitta RuthPalacios Gambra, Francisco JavierAlonso Pérez, Concepción Estibalizquinolinyl phosphonatestopoisomerase 1Benzyme inhibitionantiproliferative effectleishmaniosis effectThis 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.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.MDPI2021202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/53076reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00/info:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00/info:eu-repo/grantAgreement/MINECO/SAF2017–83575-R/https://www.mdpi.com/1424-8247/14/8/784/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:10810/530762026-06-18T09:23:17Z
dc.title.none.fl_str_mv Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
title Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
spellingShingle Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
Selas Lanseros, Asier
quinolinyl phosphonates
topoisomerase 1B
enzyme inhibition
antiproliferative effect
leishmaniosis effect
title_short Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
title_full Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
title_fullStr Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
title_full_unstemmed Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
title_sort Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)
dc.creator.none.fl_str_mv Selas Lanseros, Asier
Fuertes Sánchez, María
Melcón-Fernández, Estela
Pérez-Pertejo, Yolanda
Reguera, Rosa M.
Balaña-Fouce, Rafael
Knudsen, Birgitta Ruth
Palacios Gambra, Francisco Javier
Alonso Pérez, Concepción Estibaliz
author Selas Lanseros, Asier
author_facet Selas Lanseros, Asier
Fuertes Sánchez, María
Melcón-Fernández, Estela
Pérez-Pertejo, Yolanda
Reguera, Rosa M.
Balaña-Fouce, Rafael
Knudsen, Birgitta Ruth
Palacios Gambra, Francisco Javier
Alonso Pérez, Concepción Estibaliz
author_role author
author2 Fuertes Sánchez, María
Melcón-Fernández, Estela
Pérez-Pertejo, Yolanda
Reguera, Rosa M.
Balaña-Fouce, Rafael
Knudsen, Birgitta Ruth
Palacios Gambra, Francisco Javier
Alonso Pérez, Concepción Estibaliz
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv quinolinyl phosphonates
topoisomerase 1B
enzyme inhibition
antiproliferative effect
leishmaniosis effect
topic quinolinyl phosphonates
topoisomerase 1B
enzyme inhibition
antiproliferative effect
leishmaniosis effect
description 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.
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/10810/53076
url http://hdl.handle.net/10810/53076
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00/
info:eu-repo/grantAgreement/MCIU/RTI2018–101818-B-I00/
info:eu-repo/grantAgreement/MINECO/SAF2017–83575-R/
https://www.mdpi.com/1424-8247/14/8/784/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 15.228081

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