{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:25:18Z","timestamp":1788348318386,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish State Research Agency (AEI) of the Ministry of Science, Innovation and Universities","award":["PDI-2019-105813RB-C21"],"award-info":[{"award-number":["PDI-2019-105813RB-C21"]}]},{"DOI":"10.13039\/501100008742","name":"Camilo Jos\u00e9 Cela University","doi-asserted-by":"crossref","award":["UCJC 2023-10"],"award-info":[{"award-number":["UCJC 2023-10"]}],"id":[{"id":"10.13039\/501100008742","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008742","name":"Camilo Jos\u00e9 Cela University","doi-asserted-by":"crossref","award":["UCJC 2022-12"],"award-info":[{"award-number":["UCJC 2022-12"]}],"id":[{"id":"10.13039\/501100008742","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008742","name":"Camilo Jos\u00e9 Cela University","doi-asserted-by":"crossref","award":["UCJC 2024-12"],"award-info":[{"award-number":["UCJC 2024-12"]}],"id":[{"id":"10.13039\/501100008742","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite 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\u2014ethisterone (MC1\u20133), mifepristone (MC4\u20135) and stanolone (MC6\u20137)\u2014in an in vitro model of cerebral ischemia. Overall, these derivatives exhibited neuroprotective and antioxidant effects superior to those of the reference compounds cholesteronitrone ChN2, \u03b1-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.<\/jats:p>","DOI":"10.3390\/ijms262311506","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"11506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7491-7313","authenticated-orcid":false,"given":"Sara","family":"Izquierdo-Bermejo","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, Ciudad Universitaria, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"},{"name":"Faculty of Health Sciences\u2013HM Hospitals, Camilo Jos\u00e9 Cela University, Villafranca del Castillo, 28692 Madrid, Spain"},{"name":"Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Chioua","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), C\/Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-350X","authenticated-orcid":false,"given":"Dimitra","family":"Hadjipavlou-Litina","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5188-6038","authenticated-orcid":false,"given":"Francisco","family":"L\u00f3pez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences\u2013HM Hospitals, Camilo Jos\u00e9 Cela University, Villafranca del Castillo, 28692 Madrid, Spain"},{"name":"HM Hospitals Health Research Institute, 28015 Madrid, Spain"},{"name":"Neuropsychopharmacology Unit, \u201cHospital 12 de Octubre\u201d Research Institute, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Marco-Contelles","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), C\/Juan de la Cierva 3, 28006 Madrid, Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER), Carlos III Health Institute (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-0222","authenticated-orcid":false,"given":"Mar\u00eda Jes\u00fas","family":"Oset-Gasque","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ram\u00f3n y Cajal s\/n, Ciudad Universitaria, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"},{"name":"Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neuroscience.2024.02.017","article-title":"New Perspectives in Neuroprotection for Ischemic Stroke","volume":"550","author":"Arias","year":"2024","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, Regional, and National Burden of Stroke and its Risk Factors, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"698","DOI":"10.2174\/1871527311312050015","article-title":"Oxidative Stress and Pathophysiology of Ischemic Stroke: Novel Therapeutic Opportunities","volume":"12","author":"Rodrigo","year":"2013","journal-title":"CNS Neurol. 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