{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:29:31Z","timestamp":1762061371505,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["SAF2015-65586-R","OPTICOMC903","NACONT"],"award-info":[{"award-number":["SAF2015-65586-R","OPTICOMC903","NACONT"]}]},{"name":"Universidad Camilo Jos\u00e9 Cela","award":["SAF2015-65586-R","OPTICOMC903","NACONT"],"award-info":[{"award-number":["SAF2015-65586-R","OPTICOMC903","NACONT"]}]},{"name":"Spanish Ministry of Science, Innovation and Universities for the predoctoral FPU","award":["SAF2015-65586-R","OPTICOMC903","NACONT"],"award-info":[{"award-number":["SAF2015-65586-R","OPTICOMC903","NACONT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>We report herein the synthesis and antioxidant profile of nine novel heterobisnitrones (hBNs) as new \u03b1-phenyl-tert-butylnitrone (PBN) analogues. The synthesized hBNs 1\u20139 were evaluated for their antioxidant activity using different in vitro techniques, while they were also tested as inhibitors of soybean LOX, as an indication of their anti-inflammatory effect. Nitrone hBN9 is the most potent antioxidant presenting higher anti-lipid peroxidation and hydroxyl radicals scavenging activities as well as higher lipoxygenase inhibition. In silico calculations reveal that hBN9 follows Lipinski\u2019s rule of five and that the molecule is able to penetrate theoretically the brain. All these results led us to propose hBN9 as a new potent antioxidant nitrone.<\/jats:p>","DOI":"10.3390\/antiox11081575","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:58:08Z","timestamp":1660597088000},"page":"1575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and Antioxidant Properties of HeteroBisNitrones Derived from Benzene Dicarbaldehydes"],"prefix":"10.3390","volume":"11","author":[{"given":"Daniel","family":"Diez-Iriepa","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain"},{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Qu\u00edmica Inorg\u00e1nica, Universidad de Alcal\u00e1, Ctra. Madrid-Barcelona km 33.6, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-9624","authenticated-orcid":false,"given":"Isabel","family":"Iriepa","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Qu\u00edmica Inorg\u00e1nica, Universidad de Alcal\u00e1, Ctra. Madrid-Barcelona km 33.6, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"Institute of Chemical Research Andr\u00e9s M. del R\u00edo, Alcal\u00e1 University, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"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 of Madrid (UCJC), 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"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), CIBER, ISCIII, 46010 Madrid, Spain"}],"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"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.clineuro.2009.04.001","article-title":"The complexity of neurobiological processes in acute ischemic stroke","volume":"111","author":"Brouns","year":"2009","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5469\/neuroint.2012.7.1.1","article-title":"Safety and efficacy of mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke: A systematic review","volume":"7","author":"Koh","year":"2012","journal-title":"Neurointervention"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/83358","article-title":"The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling","volume":"7","author":"Nicole","year":"2001","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3174\/ajnr.A2006","article-title":"Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: A multicenter study","volume":"31","author":"Hussein","year":"2010","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chow, C.K. (1988). Cellular Antioxidant Defense Mechanisms, CRC Press.","DOI":"10.1016\/0891-5849(89)90105-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","article-title":"Alzheimer mechanisms and therapeutic strategies","volume":"148","author":"Huang","year":"2012","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd2896","article-title":"Alzheimer\u2019s disease: Strategies for disease modification","volume":"9","author":"Citron","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1001\/jama.2014.3654","article-title":"Pharmacological treatment of Parkinson disease","volume":"311","author":"Connolly","year":"2014","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.ejmech.2015.10.001","article-title":"Donepezi-l-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation","volume":"121","author":"Wu","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Alonso, J.M., Escobar-Peso, A., Palomino-Antol\u00edn, A., Diez-Iriepa, D., Chioua, M., Mart\u00ednez-Alonso, E., Iriepa, I., Egea, J., Alc\u00e1zar, J., and Marco-Contelles, J. (2021). Privileged quinolylnitrones for the combined therapy of ischemic stroke and Alzheimer\u2019s disease. Pharmaceuticals, 14.","DOI":"10.3390\/ph14090861"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/10715768609080971","article-title":"Phenyl-t-butyl-nitrone is active against traumatic shock in rats","volume":"1","author":"Novelli","year":"1986","journal-title":"Free Radic. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1021\/acs.joc.0c00563","article-title":"Substituted \u03b1-phenyl and \u03b1-naphthlyl-N-tert-butyl nitrones: Synthesis, spin-trapping, and neuroprotection evaluation","volume":"85","author":"Deletraz","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13413","DOI":"10.1021\/acs.jmedchem.0c00976","article-title":"Recent advances on nitrones design for stroke treatment","volume":"63","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1021\/ja011507s","article-title":"Stilbazulenyl nitrone (STAZN): A nitronyl-substituted hydrocarbon with the potency of classical phenolic chain-breaking antioxidants","volume":"124","author":"Becker","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S0891-5849(97)00338-9","article-title":"Azulenyl nitrones: Colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient forebrain ischemia\/reperfusion model","volume":"24","author":"Althaus","year":"1998","journal-title":"Free Radical Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1016\/j.bmc.2012.04.016","article-title":"Novel multi-functional nitrones for treatment of ischemic stroke","volume":"20","author":"Sun","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14150","DOI":"10.1038\/s41598-020-70690-y","article-title":"Synthesis, antioxidant properties and neuroprotection of \u03b1-phenyl-tert-butylnitrone derived homobisnitrones in in vitro and in vivo ischemia models","volume":"10","author":"Chamorro","year":"2020","journal-title":"Sci. Rep."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:08:56Z","timestamp":1760141336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":18,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["antiox11081575"],"URL":"https:\/\/doi.org\/10.3390\/antiox11081575","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}