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Volume 26
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10.3390/ijms262311506
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Sara Izquierdo-Bermejo
1,2,3,4,
Mourad Chioua
5,
Dimitra Hadjipavlou-Litina
6,
Francisco López-Muñoz
3,7,8,
José Marco-Contelles
5,9,* and
María Jesús Oset-Gasque
1,2,4,*
1
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain
2
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, 28040 Madrid, Spain
3
Faculty of Health Sciences–HM Hospitals, Camilo José Cela University, Villafranca del Castillo, 28692 Madrid, Spain
4
Instituto Universitario de Investigación en Neuroquímica, Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain
5
Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain
6
Department of Pharmaceutical Chemistry, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
7
HM Hospitals Health Research Institute, 28015 Madrid, Spain
8
Neuropsychopharmacology Unit, “Hospital 12 de Octubre” Research Institute, 28041 Madrid, Spain
9
Center for Biomedical Network Research on Rare Diseases (CIBERER), Carlos III Health Institute (ISCIII), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(23), 11506; https://doi.org/10.3390/ijms262311506
Submission received: 29 October 2025 / Revised: 24 November 2025 / Accepted: 25 November 2025 / Published: 27 November 2025
(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)
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Abstract

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—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.
Keywords: cerebral ischemia; neuroactive steroids; neuroprotection; nitrones; oxidative stress; oximes; stroke cerebral ischemia; neuroactive steroids; neuroprotection; nitrones; oxidative stress; oximes; stroke
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MDPI and ACS Style

Izquierdo-Bermejo, S.; Chioua, M.; Hadjipavlou-Litina, D.; López-Muñoz, F.; Marco-Contelles, J.; Oset-Gasque, M.J. Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro. Int. J. Mol. Sci. 2025, 26, 11506. https://doi.org/10.3390/ijms262311506

AMA Style

Izquierdo-Bermejo S, Chioua M, Hadjipavlou-Litina D, López-Muñoz F, Marco-Contelles J, Oset-Gasque MJ. Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro. International Journal of Molecular Sciences. 2025; 26(23):11506. https://doi.org/10.3390/ijms262311506

Chicago/Turabian Style

Izquierdo-Bermejo, Sara, Mourad Chioua, Dimitra Hadjipavlou-Litina, Francisco López-Muñoz, José Marco-Contelles, and María Jesús Oset-Gasque. 2025. "Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro" International Journal of Molecular Sciences 26, no. 23: 11506. https://doi.org/10.3390/ijms262311506

APA Style

Izquierdo-Bermejo, S., Chioua, M., Hadjipavlou-Litina, D., López-Muñoz, F., Marco-Contelles, J., & Oset-Gasque, M. J. (2025). Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro. International Journal of Molecular Sciences, 26(23), 11506. https://doi.org/10.3390/ijms262311506

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