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First generation of antioxidant precursors for bioisosteric Se-NSAIDs: design, synthesis, and in vitro and in vivo anticancer evaluation

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dc.contributor.authorRamos Inza, Sandra
dc.contributor.authorAliaga, César
dc.contributor.authorEncío Martínez, Ignacio
dc.contributor.authorRaza, Asif
dc.contributor.authorSharma, Arun K.
dc.contributor.authorAydillo, Carlos
dc.contributor.authorMartínez-Sáez, Nuria
dc.contributor.authorSanmartín, Carmen
dc.contributor.authorPlano, Daniel
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2024-05-10T13:34:46Z
dc.date.available2024-05-10T13:34:46Z
dc.date.issued2023
dc.date.updated2024-05-10T13:17:45Z
dc.description.abstractThe introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay. The new Se-NSAID derivatives bearing this unique combination showed antioxidant activity in a time- and dose-dependent manner, and also displayed different antiproliferative profiles in a panel of eight cancer cell lines as determined by the MTT assay. Ibuprofen derivative 5 was not only the most antioxidant agent, but also selectively induced toxicity in all the cancer cell lines tested (IC50 < 10 µM) while sparing nonmalignant cells, and induced apoptosis partially without enhancing the caspase 3/7 activity. Furthermore, NSAID derivative 5 significantly suppressed tumor growth in a subcutaneous colon cancer xenograft mouse model (10 mg/kg, TGI = 72%, and T/C = 38%) without exhibiting any apparent toxicity. To our knowledge, this work constitutes the first report on in vitro and in vivo anticancer activity of an unprecedented Se-NSAID hybrid derivative and its rational use for developing precursors for bioisosteric selenocompounds with appealing therapeutic applications.en
dc.description.sponsorshipThis research was financially supported by the Plan de Investigación de la Universidad de Navarra, PIUNA (2018-19), and the Department of Pharmacology and Penn State Cancer Institute of the Penn State College of Medicine.; Sandra Ramos-Inza acknowledges the support of the FPU program from the Spanish Ministry of Universities for a Ph.D. fellowship (FPU18/04679) and a mobility grant (EST19/00898).en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRamos-Inza, S., Aliaga, C., Encío, I., Raza, A., Sharma, A. K., Aydillo, C., Martínez-Sáez, N., Sanmartín, C., Plano, D. (2023) First generation of antioxidant precursors for bioisosteric Se-NSAIDs: Design, synthesis, and in vitro and in vivo anticancer evaluation. Antioxidants, 12(9), 1-21. https://doi.org/10.3390/antiox12091666.en
dc.identifier.doi10.3390/antiox12091666
dc.identifier.issn2076-3921
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48100
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofAntioxidants 2023, 12(9), 1666en
dc.relation.publisherversionhttps://doi.org/10.3390/antiox12091666
dc.rights© 2023 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.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntioxidanten
dc.subjectAntiproliferative agentsen
dc.subjectColon canceren
dc.subjectDiacyl diselenideen
dc.subjectMouse xenograft modelen
dc.subjectNSAIDen
dc.subjectSeleniumen
dc.titleFirst generation of antioxidant precursors for bioisosteric Se-NSAIDs: design, synthesis, and in vitro and in vivo anticancer evaluationen
dc.typeinfo:eu-repo/semantics/article
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
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relation.isAuthorOfPublication599ca381-1fd2-4a23-93ab-4373837eb6e0
relation.isAuthorOfPublication.latestForDiscovery599ca381-1fd2-4a23-93ab-4373837eb6e0

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