Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro

This article belongs to the Special Issue Targeted Pharmacological Modulation of Cellular Pathology and Drug Discovery: A Translational Approach to Bridge Laboratory Discoveries with Clinical Practice

Detalles Bibliográficos
Autores: Izquierdo-Bermejo, Sara, Chioua, Mourad, Hadjipavlou-Litina, Dimitra, López-Muñoz, Francisco, Marco-Contelles, José, Oset-Gasque, María Jesús
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:10261/408545
Acceso en línea:http://hdl.handle.net/10261/408545
Access Level:acceso abierto
Palabra clave:Cerebral ischemia
Neuroactive steroids
Neuroprotection
Nitrones
Oxidative stress
Oximes
Stroke
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spelling Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In VitroIzquierdo-Bermejo, SaraChioua, MouradHadjipavlou-Litina, DimitraLópez-Muñoz, FranciscoMarco-Contelles, JoséOset-Gasque, María JesúsCerebral ischemiaNeuroactive steroidsNeuroprotectionNitronesOxidative stressOximesStrokeThis article belongs to the Special Issue Targeted Pharmacological Modulation of Cellular Pathology and Drug Discovery: A Translational Approach to Bridge Laboratory Discoveries with Clinical PracticeDespite the substantial global impact of ischemic stroke, current therapeutic options remain limited and only partially effective. To advance neuroprotective strategies that could improve the safety and efficacy of existing treatments while preserving brain tissue, we synthesized and evaluated seven new nitrones (MC3, MC5, MC7) and oximes (MC1, MC2, MC4, MC6) derived from different neuroactive steroids—ethisterone (MC1–3), mifepristone (MC4–5) and stanolone (MC6–7)—in an in vitro model of cerebral ischemia. Overall, these derivatives exhibited neuroprotective and antioxidant effects superior to those of the reference compounds cholesteronitrone ChN2, α-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC). Notably, nitrones showed greater neuroprotective, anti-necrotic, and antioxidant potency than their corresponding oximes, regardless of the degree of molecular conjugation. Among them, the stanolone-derived nitrone MC7, which lacks conjugated double bonds, displayed the most balanced and robust profile, consistently enhancing cell viability, reducing necrotic cell death, and suppressing superoxide anion production. Consequently, MC7 has been selected as a promising lead compound for further in vivo studies of cerebral ischemia.This research was supported by grants from the Spanish State Research Agency (AEI) of the Ministry of Science, Innovation and Universities (MICINN) (PDI-2019-105813RB-C21) to J.M-C., and from Camilo José Cela University (UCJC) Grants “CHONICEN” (UCJC 2023-10), “NENS” (UCJC 2022-12) and “HDACi-Stroke” (UCJC 2024-12) to M.J.O.-G. and J.M-C.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Universidad Camilo José CelaChioua, Mourad [0000-0002-8016-5459]Marco-Contelles, José [0000-0003-0690-0328]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/408545reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//PDI-2019-105813RB-C21The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ijms262311506https://doi.org/10.3390/ijms262311506Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4085452026-05-22T06:33:51Z
dc.title.none.fl_str_mv Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
title Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
spellingShingle Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
Izquierdo-Bermejo, Sara
Cerebral ischemia
Neuroactive steroids
Neuroprotection
Nitrones
Oxidative stress
Oximes
Stroke
title_short Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
title_full Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
title_fullStr Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
title_full_unstemmed Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
title_sort Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro
dc.creator.none.fl_str_mv Izquierdo-Bermejo, Sara
Chioua, Mourad
Hadjipavlou-Litina, Dimitra
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author Izquierdo-Bermejo, Sara
author_facet Izquierdo-Bermejo, Sara
Chioua, Mourad
Hadjipavlou-Litina, Dimitra
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author_role author
author2 Chioua, Mourad
Hadjipavlou-Litina, Dimitra
López-Muñoz, Francisco
Marco-Contelles, José
Oset-Gasque, María Jesús
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Universidad Camilo José Cela
Chioua, Mourad [0000-0002-8016-5459]
Marco-Contelles, José [0000-0003-0690-0328]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cerebral ischemia
Neuroactive steroids
Neuroprotection
Nitrones
Oxidative stress
Oximes
Stroke
topic Cerebral ischemia
Neuroactive steroids
Neuroprotection
Nitrones
Oxidative stress
Oximes
Stroke
description This article belongs to the Special Issue Targeted Pharmacological Modulation of Cellular Pathology and Drug Discovery: A Translational Approach to Bridge Laboratory Discoveries with Clinical Practice
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
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/10261/408545
url http://hdl.handle.net/10261/408545
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/AEI//PDI-2019-105813RB-C21
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ijms262311506
https://doi.org/10.3390/ijms262311506
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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 15,81155

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