Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases

We synthesised coumarin-based derivatives bearing thio- and selenocyanates to selectively inhibit tumour-associated carbonic anhydrases (CAs) IX and XII and to exert antiproliferative effects on tumour cells. Structural variations included chalcogen atom type (S, Se), substitutions at C-3/C-4, and t...

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Autores: Meza-Ireta, Silvia Alejandra, Romero-Hernández, Laura L., Begines, Paloma, Giouvannuzi, Simone, Puerta, Adrián, González-Bakker, Aday, Romero-Franco, Amador, Huertas, Pablo, Nocentini, Alessio, Vega-Báez, José Luis, Montiel-Smith, Sara, Fernández-Bolaños, José G., Castellano-Pozo, Maikel, Padrón, José M, Supuran, Claudiu T., Merino-Montiel, Penélope, López, Óscar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/412199
Acceso en línea:http://hdl.handle.net/10261/412199
https://api.elsevier.com/content/abstract/scopus_id/105021200157
Access Level:acceso abierto
Palabra clave:C. elegans
Antiproliferative agents
Carbonic anhydrases
Coumarins
Organoselenium
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spelling Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrasesMeza-Ireta, Silvia AlejandraRomero-Hernández, Laura L.Begines, PalomaGiouvannuzi, SimonePuerta, AdriánGonzález-Bakker, AdayRomero-Franco, AmadorHuertas, PabloNocentini, AlessioVega-Báez, José LuisMontiel-Smith, SaraFernández-Bolaños, José G.Castellano-Pozo, MaikelPadrón, José MSupuran, Claudiu T.Merino-Montiel, PenélopeLópez, ÓscarC. elegansAntiproliferative agentsCarbonic anhydrasesCoumarinsOrganoseleniumWe synthesised coumarin-based derivatives bearing thio- and selenocyanates to selectively inhibit tumour-associated carbonic anhydrases (CAs) IX and XII and to exert antiproliferative effects on tumour cells. Structural variations included chalcogen atom type (S, Se), substitutions at C-3/C-4, and tether length at C-7 of the coumarin core. Thiocyanates 4 and 7b showed potent CA IX/XII inhibition (Ki = 17.9-27.4 nM) with >5000-fold selectivity over off-target isoforms (CAs I and II). Selenocyanate 8a exhibited strong antiproliferative activity (GI50 = 0.78-2.6 µM) across six human solid tumour cell lines. Mechanistic studies revealed a cytostatic effect via cell cycle arrest and reduced mitotic progression. In vivo assays in Caenorhabditis elegans confirmed selective cytostatic action of selenocyanate 8c, reducing tumorous germline size without affecting healthy tissues at therapeutic doses.J.G.F.-B. and Ó.L. thank Junta de Andalucía (FQM134) and VII Plan Propio de Investigación (University of Seville). P.M.-M. thanks VIEP-BUAP (Ref. 00664-PV/2025). L.L.R.-H. thanks the Mexican SECIHTI for the award of a postdoctoral fellowship (I1200/311/2023, MOD.ORD./08/2023). M.C.-P. thanks European MSCA IF (grant coDNAres 101023902). P.B. thanks the European Union (NextGenerationEU) and the Ministerio de Universidades of Spain (Grant Margarita Salas). A.P. thanks the EU Social Fund (FSE) and the Canary Islands ACIISI for a predoctoral grant TESIS2020010055. A.G.-B. thanks the Asociación Española Contra el Cáncer (AECC) de Santa Cruz de Tenerife for predoctoral grant PRDTF233958GONZ.Peer reviewedTaylor & FrancisJunta de AndalucíaUniversidad de SevillaEuropean CommissionMinisterio de Universidades (España)Asociación Española Contra el CáncerRomero-Franco, Amador [0000-0003-3212-1643]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/412199https://api.elsevier.com/content/abstract/scopus_id/105021200157reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/101023902Meza-Ireta, Silvia Alejandra; Romero-Hernández, Laura L.; Begines, Paloma; Giouvannuzi, Simone; Puerta, Adrián; González-Bakker, Aday; Romero-Franco, Amador; Huertas, Pablo; Nocentini, Alessio; Vega-Báez, José Luis; Montiel-Smith, Sara; Fernández-Bolaños, José G.; Castellano-Pozo, Maikel; Padrón, José M; Supuran, Claudiu T.; Merino-Montiel, Penélope; López, Óscar; 2025; Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases [Dataset]; Figshare; https://doi.org/10.6084/m9.figshare.30580742https://doi.org/10.1080/14756366.2025.2578183Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4121992026-05-22T06:33:51Z
dc.title.none.fl_str_mv Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
title Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
spellingShingle Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
Meza-Ireta, Silvia Alejandra
C. elegans
Antiproliferative agents
Carbonic anhydrases
Coumarins
Organoselenium
title_short Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
title_full Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
title_fullStr Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
title_full_unstemmed Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
title_sort Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
dc.creator.none.fl_str_mv Meza-Ireta, Silvia Alejandra
Romero-Hernández, Laura L.
Begines, Paloma
Giouvannuzi, Simone
Puerta, Adrián
González-Bakker, Aday
Romero-Franco, Amador
Huertas, Pablo
Nocentini, Alessio
Vega-Báez, José Luis
Montiel-Smith, Sara
Fernández-Bolaños, José G.
Castellano-Pozo, Maikel
Padrón, José M
Supuran, Claudiu T.
Merino-Montiel, Penélope
López, Óscar
author Meza-Ireta, Silvia Alejandra
author_facet Meza-Ireta, Silvia Alejandra
Romero-Hernández, Laura L.
Begines, Paloma
Giouvannuzi, Simone
Puerta, Adrián
González-Bakker, Aday
Romero-Franco, Amador
Huertas, Pablo
Nocentini, Alessio
Vega-Báez, José Luis
Montiel-Smith, Sara
Fernández-Bolaños, José G.
Castellano-Pozo, Maikel
Padrón, José M
Supuran, Claudiu T.
Merino-Montiel, Penélope
López, Óscar
author_role author
author2 Romero-Hernández, Laura L.
Begines, Paloma
Giouvannuzi, Simone
Puerta, Adrián
González-Bakker, Aday
Romero-Franco, Amador
Huertas, Pablo
Nocentini, Alessio
Vega-Báez, José Luis
Montiel-Smith, Sara
Fernández-Bolaños, José G.
Castellano-Pozo, Maikel
Padrón, José M
Supuran, Claudiu T.
Merino-Montiel, Penélope
López, Óscar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Junta de Andalucía
Universidad de Sevilla
European Commission
Ministerio de Universidades (España)
Asociación Española Contra el Cáncer
Romero-Franco, Amador [0000-0003-3212-1643]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv C. elegans
Antiproliferative agents
Carbonic anhydrases
Coumarins
Organoselenium
topic C. elegans
Antiproliferative agents
Carbonic anhydrases
Coumarins
Organoselenium
description We synthesised coumarin-based derivatives bearing thio- and selenocyanates to selectively inhibit tumour-associated carbonic anhydrases (CAs) IX and XII and to exert antiproliferative effects on tumour cells. Structural variations included chalcogen atom type (S, Se), substitutions at C-3/C-4, and tether length at C-7 of the coumarin core. Thiocyanates 4 and 7b showed potent CA IX/XII inhibition (Ki = 17.9-27.4 nM) with >5000-fold selectivity over off-target isoforms (CAs I and II). Selenocyanate 8a exhibited strong antiproliferative activity (GI50 = 0.78-2.6 µM) across six human solid tumour cell lines. Mechanistic studies revealed a cytostatic effect via cell cycle arrest and reduced mitotic progression. In vivo assays in Caenorhabditis elegans confirmed selective cytostatic action of selenocyanate 8c, reducing tumorous germline size without affecting healthy tissues at therapeutic doses.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/412199
https://api.elsevier.com/content/abstract/scopus_id/105021200157
url http://hdl.handle.net/10261/412199
https://api.elsevier.com/content/abstract/scopus_id/105021200157
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/101023902
Meza-Ireta, Silvia Alejandra; Romero-Hernández, Laura L.; Begines, Paloma; Giouvannuzi, Simone; Puerta, Adrián; González-Bakker, Aday; Romero-Franco, Amador; Huertas, Pablo; Nocentini, Alessio; Vega-Báez, José Luis; Montiel-Smith, Sara; Fernández-Bolaños, José G.; Castellano-Pozo, Maikel; Padrón, José M; Supuran, Claudiu T.; Merino-Montiel, Penélope; López, Óscar; 2025; Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases [Dataset]; Figshare; https://doi.org/10.6084/m9.figshare.30580742
https://doi.org/10.1080/14756366.2025.2578183
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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