{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T11:16:01Z","timestamp":1775301361593,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre of Lodz (Poland)","award":["UMO-2013\/11\/N\/NZ7\/00723"],"award-info":[{"award-number":["UMO-2013\/11\/N\/NZ7\/00723"]}]},{"name":"Medical University of Lodz","award":["503\/3-014-01\/503-31-001"],"award-info":[{"award-number":["503\/3-014-01\/503-31-001"]}]},{"name":"MINECO (Spain)","award":["SAF2015-65586-R"],"award-info":[{"award-number":["SAF2015-65586-R"]}]},{"name":"Universidad Camilo Jos\u00e9 Cela (Madrid) Spain","award":["UCJC 2015-12 and UCJC 2020-03"],"award-info":[{"award-number":["UCJC 2015-12 and UCJC 2020-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a\u2013i. The neuroprotective properties of nitrones, 9a\u2013i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a\u2013i, have better neuroprotective and antioxidant properties than \u03b1-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC50 values in the range of 1\u20136 \u03bcM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC50\u2032s \u2248 2\u20134 \u03bcM) and antioxidant (EC50\u2032s \u2248 0.4\u20133.5 \u03bcM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and\/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies.<\/jats:p>","DOI":"10.3390\/ijms23063411","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"3411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia\u2013Reperfusion"],"prefix":"10.3390","volume":"23","author":[{"given":"Beatriz","family":"Chamorro","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":"Faculty of Health, Camilo Jos\u00e9 Cela University, Castillo de Alarc\u00f3n 49, Villanueva de la Ca\u00f1ada, 28692 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7567-5860","authenticated-orcid":false,"given":"Iwona E.","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Gotkowska","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-707X","authenticated-orcid":false,"given":"Rafa\u0142","family":"Gulej","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-350X","authenticated-orcid":false,"given":"Dimitra","family":"Hadjipavlou-Litina","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Camilo Jos\u00e9 Cela University, Castillo de Alarc\u00f3n 49, Villanueva de la Ca\u00f1ada, 28692 Madrid, Spain"},{"name":"Neuropsychopharmacology Unit, \u201cHospital 12 de Octubre\u201d Research Institute, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Marco-Contelles","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-8796","authenticated-orcid":false,"given":"Dorota G.","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 en Neuroqu\u00edmica, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1002\/ana.10483","article-title":"Oxidative stress in Parkinson\u2019s disease","volume":"53","author":"Jenner","year":"2003","journal-title":"Ann. 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