{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:43:21Z","timestamp":1769071401967,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T00:00:00Z","timestamp":1584144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Council of Franche-Comt\u00e9","award":["2016YC-04540 and 04560"],"award-info":[{"award-number":["2016YC-04540 and 04560"]}]},{"name":"Foundation for Science and Technology; FEDER\/COMPETE","award":["UID\/QUI\/00081\/2020, PTDC\/MED-QUI\/29164\/2017, and SFRH\/BPD\/114945\/2016"],"award-info":[{"award-number":["UID\/QUI\/00081\/2020, PTDC\/MED-QUI\/29164\/2017, and SFRH\/BPD\/114945\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca2+ channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs 3a\u2013t, resulting from the juxtaposition of nimodipine, a Ca2+ channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6\u2013dimethyl\u20134-[4-(prop\u20132\u2013yn\u20131-yloxy)phenyl]-1,4-dihydro- pyridine- 3,5-dicarboxylate (3a), as an attractive antioxidant (1.75 TE), Ca2+ channel antagonist (46.95% at 10 \u03bcM), showing significant neuroprotection (38%) against H2O2 at 10 \u03bcM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer\u2019s disease agents.<\/jats:p>","DOI":"10.3390\/molecules25061329","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T07:29:07Z","timestamp":1584689347000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels"],"prefix":"10.3390","volume":"25","author":[{"given":"Irene","family":"Pach\u00f2n Angona","sequence":"first","affiliation":[{"name":"Neurosciences Int\u00e9gratives et Cliniques EA 481, P\u00f4le de Chimie Organique et Th\u00e9rapeutique, Univ. Bourgogne Franche-Comt\u00e9, UFR Sant\u00e9, 19, rue Ambroise Par\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solene","family":"Daniel","sequence":"additional","affiliation":[{"name":"Neurosciences Int\u00e9gratives et Cliniques EA 481, P\u00f4le de Chimie Organique et Th\u00e9rapeutique, Univ. Bourgogne Franche-Comt\u00e9, UFR Sant\u00e9, 19, rue Ambroise Par\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-3858","authenticated-orcid":false,"given":"Helene","family":"Martin","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, Laboratoire de Toxicologie Cellulaire, Univ. Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Bonet","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, Laboratoire de Toxicologie Cellulaire, Univ. Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-4225","authenticated-orcid":false,"given":"Artur","family":"Wnorowski","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-2544","authenticated-orcid":false,"given":"Maciej","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"J\u00f3\u017awiak","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago Barros","family":"Silva","sequence":"additional","affiliation":[{"name":"CIQUP\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre 1021\/1055, 4169-007 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Refouvelet","sequence":"additional","affiliation":[{"name":"Neurosciences Int\u00e9gratives et Cliniques EA 481, P\u00f4le de Chimie Organique et Th\u00e9rapeutique, Univ. Bourgogne Franche-Comt\u00e9, UFR Sant\u00e9, 19, rue Ambroise Par\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2402","authenticated-orcid":false,"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[{"name":"CIQUP\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre 1021\/1055, 4169-007 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Marco-Contelles","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (IQOG, CSIC), Juan de la Cierva, 3, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lhassane","family":"Ismaili","sequence":"additional","affiliation":[{"name":"Neurosciences Int\u00e9gratives et Cliniques EA 481, P\u00f4le de Chimie Organique et Th\u00e9rapeutique, Univ. Bourgogne Franche-Comt\u00e9, UFR Sant\u00e9, 19, rue Ambroise Par\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.7046051","article-title":"The cholinergic hypothesis of geriatric memory dysfunction","volume":"217","author":"Bartus","year":"1982","journal-title":"Science"},{"key":"ref_2","first-page":"1","article-title":"The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer\u2019s disease (review of Technology Appraisal No. 111): A systematic review and economic model","volume":"16","author":"Bond","year":"2012","journal-title":"Heal. Technol. 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