{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:59:43Z","timestamp":1777496383409,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We report herein the design, synthesis, biological evaluation, and molecular modelling of new inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), able to block Ca+2 channels also showing antioxidant and neuroprotective activities. The new MTDL, dialkyl 2,6-dimethyl-4-(4-((5-aminoalkyl)oxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate 3a-p, have been obtained via Hantzsch reaction from appropriate and commercially available precursors. Pertinent biological analysis has prompted us to identify MTDL 3h [dimethyl-4-(4-((5-(4-benzylpiperidin-1-yl)pentyl)oxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] as an attractive inhibitor of AChE (1.8 \u03bcM) and BuChE (2 \u03bcM), Ca+2 channel antagonist (47.72% at 10 \u03bcM), and antioxidant (2.54 TE) agent, showing significant neuroprotection 28.68% and 38.29% against H2O2, and O\/R, respectively, at 0.3 \u03bcM, thus being considered a hit-compound for further investigation in our search for anti-Alzheimer\u2019s disease agents.<\/jats:p>","DOI":"10.3390\/ijms21207652","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T08:56:48Z","timestamp":1602838608000},"page":"7652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives"],"prefix":"10.3390","volume":"21","author":[{"given":"Irene","family":"Pach\u00f3n 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"}]},{"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":"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"}]},{"given":"Ignacio","family":"Moraleda","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Inorganic Chemistry, School Sciences, University of Alcal\u00e1, Ctra. Barcelona, Km. 33.6, 28871 Alcal\u00e1 de Henares, Spain"}],"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":"Jozwiak","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\/0000-0003-3475-9624","authenticated-orcid":false,"given":"Isabel","family":"Iriepa","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Inorganic Chemistry, School Sciences, University of Alcal\u00e1, Ctra. Barcelona, Km. 33.6, 28871 Alcal\u00e1 de Henares, Spain"}],"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"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-3150","authenticated-orcid":false,"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":[[2020,10,16]]},"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":"421","article-title":"The genetic landscape of Alzheimer disease: Clinical implications and perspectives","volume":"18","author":"Sleegers","year":"2015","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.trci.2018.03.009","article-title":"Alzheimer\u2019s disease drug development pipeline: 2018","volume":"4","author":"Cummings","year":"2018","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. 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