Novel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy

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dc.authoridComert Onder, Ferah/0000-0002-4037-1979
dc.authoridAY, Mehmet/0000-0002-1095-1614
dc.contributor.authorOnder, Ferah Comert
dc.contributor.authorSiyah, Pinar
dc.contributor.authorDurdagi, Serdar
dc.contributor.authorAy, Mehmet
dc.contributor.authorOzpolat, Bulent
dc.date.accessioned2025-01-27T20:14:13Z
dc.date.available2025-01-27T20:14:13Z
dc.date.issued2022
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractEukaryotic elongation factor 2 kinase (eEF2K) has been shown to be an important molecular driver of tumorigenesis and validated as a potential novel molecular target in various solid cancers including triple negative breast cancer (TNBC). Therefore, there has been significant interest in identifying novel inhibitors of eEF2K for the development of targeted therapeutics and clinical translation. Herein, we investigated the effects of indole ring containing derivatives of etodolac, a nonsteroidal anti-inflammatory (NSAID) drug, as potential eEF2K inhibitors and we designed and synthesized seven novel compounds with a pyrano[3,4-b] indole core structure. We evaluated the eEF2K inhibitory activity of seven of these novel compounds using in silico molecular modeling and in vitro studies in TNBC cell lines. We identified two novel compounds (EC1 and EC7) with significant in vitro activity in inhibiting eEF2K in TNBC cells. In conclusion, our studies indicate that pyrano[3,4-b] indole scaffold containing compounds demonstrate marked eEF2K inhibitory activity and they may be used as eEF2K inhibitors for the development of eEF2K-targeted therapeutics.
dc.identifier.doi10.1039/d2md00105e
dc.identifier.endpage849
dc.identifier.issn2632-8682
dc.identifier.issue7
dc.identifier.pmid35923718
dc.identifier.scopus2-s2.0-85133606029
dc.identifier.scopusqualityQ2
dc.identifier.startpage840
dc.identifier.urihttps://doi.org/10.1039/d2md00105e
dc.identifier.urihttps://hdl.handle.net/20.500.12428/20999
dc.identifier.volume13
dc.identifier.wosWOS:000818031900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofRsc Medicinal Chemistry
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectAnticancer Agents
dc.subjectIndole-Derivatives
dc.subjectR-Enantiomer
dc.subjectFactor-Ii
dc.subjectProtein
dc.subjectPolymerase
dc.subjectDocking
dc.subjectPhosphorylation
dc.subjectProliferation
dc.subjectCytotoxicity
dc.titleNovel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy
dc.typeArticle

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