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The newly synthesized nitrone derivatives were firstly investigated for their activity in decreasing the level of hydroxyl radicals generated during 6\u2010OHDA oxidation, and inhibit lipid peroxidation (TBARS assay) and protein carbonyl content (PCC) in rat brain mitochondria. Most of the studied 2\u2010benzazepine nitrones showed inhibitory potencies in both TBARS and PCC assays at least two magnitude orders higher than that of PBN. The data obtained usefully complemented the known structure\u2013activity relationships. In particular, <jats:bold>5<\/jats:bold> and <jats:bold>10<\/jats:bold>, bearing C\u20103 spiro cyclopentyl and tetrahydropyranyl moieties, respectively, at 8\u2009\u00b5M concentration proved to be significantly more effective than PBN in protecting cultured DA neurons exposed to 6\u2010OHDA, which alone causes about 45% cell loss in 24\u2009h. In addition, we found that <jats:bold>5<\/jats:bold> inhibited butyrylcholinesterase with an IC<jats:sub>50<\/jats:sub> value of 16.8\u2009\u00b5M, which would enhance its potential as neuroprotective agent in Alzheimer's neurodegeneration. These findings extend the utility of benzazepine\u2010based PBN analogs in the treatment of age\u2010related free radical\u2010mediated disorders.<\/jats:p>","DOI":"10.1002\/ardp.201200007","type":"journal-article","created":{"date-parts":[[2012,4,25]],"date-time":"2012-04-25T11:04:41Z","timestamp":1335351881000},"page":"598-609","source":"Crossref","is-referenced-by-count":17,"title":["2\u2010Benzazepine Nitrones Protect Dopaminergic Neurons against 6\u2010Hydroxydopamine\u2010Induced Oxidative Toxicity"],"prefix":"10.1002","volume":"345","author":[{"given":"Ram\u00f3n","family":"Soto\u2010Otero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"M\u00e9ndez\u2010\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda","family":"S\u00e1nchez\u2010Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Lu\u00eds","family":"Labandeira\u2010Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannette","family":"Rodr\u00edguez\u2010Pallares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor I.","family":"Zubkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir P.","family":"Zaytsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid G.","family":"Voskressensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey V.","family":"Varlamov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modesto","family":"de Candia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Fiorella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Altomare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,25]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.08.017"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.025"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715760600918142"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200317100-00004"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(01)00385-2"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.11.10.1407"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200418150-00003"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1368-5031.2004.00245.x"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.143479"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm100212x"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx900114v"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00270-1"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00904-0"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02101-0"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3097"},{"key":"e_1_2_5_17_2","doi-asserted-by":"crossref","first-page":"28055","DOI":"10.1016\/S0021-9258(18)46894-9","volume":"269","author":"Thomas C. 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