{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T14:51:12Z","timestamp":1794408672574,"version":"4.9.0"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Council of Franche-Comt\u00e9","award":["2022Y-13659"],"award-info":[{"award-number":["2022Y-13659"]}]},{"name":"Regional Council of Franche-Comt\u00e9","award":["13660"],"award-info":[{"award-number":["13660"]}]},{"name":"CERMN (Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie)","award":["2022Y-13659"],"award-info":[{"award-number":["2022Y-13659"]}]},{"name":"CERMN (Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie)","award":["13660"],"award-info":[{"award-number":["13660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Novel multitarget-directed ligands BIGI 4a-d and BIGI\u00a05a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-\/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.<\/jats:p>","DOI":"10.3390\/molecules28010071","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:31:11Z","timestamp":1671676271000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation"],"prefix":"10.3390","volume":"28","author":[{"given":"Rim","family":"Malek","sequence":"first","affiliation":[{"name":"Laboratoire LINC UR 481, P\u00f4le de Chimie M\u00e9dicinale, University Franche-Comt\u00e9, UFR Sant\u00e9, 19, rue Ambroise Par\u00e9, F-25000 Besan\u00e7on, France"},{"name":"Laboratory of Applied Chemistry: Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, Sfax 3000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3076-0030","authenticated-orcid":false,"given":"Alexey","family":"Simakov","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, University Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-2380","authenticated-orcid":false,"given":"Audrey","family":"Davis","sequence":"additional","affiliation":[{"name":"Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, ul. 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Chodzki 4a, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-3858","authenticated-orcid":false,"given":"Helene","family":"Martin","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, University Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Marco-Contelles","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (IQOG, CSIC), C\/ Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakher","family":"Chabchoub","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Chemistry: Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, Sfax 3000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-615X","authenticated-orcid":false,"given":"Patrick","family":"Dallemagne","sequence":"additional","affiliation":[{"name":"Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-2082","authenticated-orcid":false,"given":"Christophe","family":"Rochais","sequence":"additional","affiliation":[{"name":"Centre d\u2019Etudes et de Recherche sur le M\u00e9dicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-5092","authenticated-orcid":false,"given":"Krzysztof","family":"Jozwiak","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, ul. 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