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Chromenone derivatives as CRM1 inhibitors for targeting glioblastoma

2025-06-27Artigo científico Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
datacite.subject.sdg09:Indústria, Inovação e Infraestruturas
datacite.subject.sdg04:Educação de Qualidade
dc.contributor.authorPrinciotto, Salvatore
dc.contributor.authorJiménez, Lucía
dc.contributor.authorDomínguez, Lucía
dc.contributor.authorSequeira, João G. N.
dc.contributor.authorMourato Paulo, Cristiana Isabel
dc.contributor.authorOrea-Soufi, Alba
dc.contributor.authorda Silva Santos, Bruno Filipe
dc.contributor.authorDallavalle, Sabrina
dc.contributor.authorMachuqueiro, Miguel
dc.contributor.authorferreira, Bibiana
dc.contributor.authorLink, Wolfgang
dc.date.accessioned2026-03-27T10:13:22Z
dc.date.available2026-03-27T10:13:22Z
dc.date.issued2025-06-27
dc.description.abstractGlioblastoma (GBM) is one of the most aggressive and deadly cancers. Due to the complexity and redundancy within signaling networks in GBM, targeted inhibitors of specific pathways have shown only limited success. The nuclear export receptor chromosome region maintenance 1 (CRM1) has recently emerged as a promising therapeutic target, as its inhibition can simultaneously disrupt multiple key oncogenic drivers. Herein, whether chromenone derivatives, known for detecting thiol-containing molecules, can function as CRM1 inhibitors is explored. Several chromenonebased derivatives are synthesized and it is demonstrated that they inhibit CRM1-driven nuclear export in a structure- and dose-dependent manner. A preliminary structure–activity relationship is established, providing a rationale for selective CRM1 binding based on molecular docking studies. Additionally, it is showed that the active chromenone derivatives effectively inhibit the nuclear export of endogenous nuclear export signal-containing substrates in GBM cells. Several of these compounds exhibit selective cytotoxicity againstGBM cell lines, highlighting their potential as targeted therapies for GBM.eng
dc.description.sponsorship2022.10517; 2023.10710; CEECIND/02300/2017; PID2022‐136654OB‐I00
dc.identifier.doi10.1002/cbic.202500195
dc.identifier.eissn1439-7633
dc.identifier.issn1439-4227
dc.identifier.urihttp://hdl.handle.net/10400.1/28555
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relationBiosystems and Integrative Sciences Institute
dc.relationBiosystems and Integrative Sciences Institute
dc.relationPID2022‐136654OB‐I00
dc.relation.ispartofChemBioChem
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectChromenone
dc.subjectChromosome region maintenance 1/ XPO1
dc.subjectExportin 1
dc.subjectGlioblastoma
dc.subjectMolecular docking
dc.subjectNuclear export inhibitors
dc.titleChromenone derivatives as CRM1 inhibitors for targeting glioblastomaeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberUIDP/04046/2020
oaire.awardNumberUIDB/04046/2020
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT
oaire.citation.issue15
oaire.citation.startPagee20250019
oaire.citation.titleChemBioChem
oaire.citation.volume26
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameMourato Paulo
person.familyNameOrea-Soufi
person.familyNameda Silva Santos
person.familyNameferreira
person.givenNameCristiana Isabel
person.givenNameAlba
person.givenNameBruno Filipe
person.givenNameBibiana
person.identifier.ciencia-id3B1A-A815-4188
person.identifier.ciencia-id6C16-45B1-8301
person.identifier.ciencia-id9F19-3184-159F
person.identifier.ciencia-idA311-E925-09C5
person.identifier.orcid0000-0003-1402-9747
person.identifier.orcid0000-0001-9264-6519
person.identifier.orcid0000-0003-4772-9395
person.identifier.scopus-author-id56964305800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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