Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
Novel multitarget-directed ligands <b>BIGI 4a-d</b> and <b>BIGI 5a-d</b> 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,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/1/71 |
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| author | Rim Malek Alexey Simakov Audrey Davis Maciej Maj Paul J. Bernard Artur Wnorowski Helene Martin José Marco-Contelles Fakher Chabchoub Patrick Dallemagne Christophe Rochais Krzysztof Jozwiak Lhassane Ismaili |
| author_facet | Rim Malek Alexey Simakov Audrey Davis Maciej Maj Paul J. Bernard Artur Wnorowski Helene Martin José Marco-Contelles Fakher Chabchoub Patrick Dallemagne Christophe Rochais Krzysztof Jozwiak Lhassane Ismaili |
| author_sort | Rim Malek |
| collection | DOAJ |
| description | Novel multitarget-directed ligands <b>BIGI 4a-d</b> and <b>BIGI 5a-d</b> 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, <b>BIGI 4b</b>, <b>BIGI 4d,</b> and <b>BIGI 5b</b> 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. |
| first_indexed | 2024-03-09T03:30:49Z |
| format | Article |
| id | doaj.art-c1008cfa0311472f9605360beca986c5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T03:30:49Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c1008cfa0311472f9605360beca986c52023-12-03T14:56:25ZengMDPI AGMolecules1420-30492022-12-012817110.3390/molecules28010071Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 ActivationRim Malek0Alexey Simakov1Audrey Davis2Maciej Maj3Paul J. Bernard4Artur Wnorowski5Helene Martin6José Marco-Contelles7Fakher Chabchoub8Patrick Dallemagne9Christophe Rochais10Krzysztof Jozwiak11Lhassane Ismaili12Laboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, FrancePEPITE EA4267, University Franche-Comté, F-25000 Besançon, FranceCentre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, FranceDepartment of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, PolandLaboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, FranceDepartment of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, PolandPEPITE EA4267, University Franche-Comté, F-25000 Besançon, FranceLaboratory of Medicinal Chemistry (IQOG, CSIC), C/ Juan de la Cierva 3, 28006 Madrid, SpainLaboratory of Applied Chemistry: Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, Sfax 3000, TunisiaCentre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, FranceCentre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, FranceDepartment of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, PolandLaboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, FranceNovel multitarget-directed ligands <b>BIGI 4a-d</b> and <b>BIGI 5a-d</b> 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, <b>BIGI 4b</b>, <b>BIGI 4d,</b> and <b>BIGI 5b</b> 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.https://www.mdpi.com/1420-3049/28/1/71Biginelli reactionmultitarget-directed ligandscalcium channel antagonismNrf2 |
| spellingShingle | Rim Malek Alexey Simakov Audrey Davis Maciej Maj Paul J. Bernard Artur Wnorowski Helene Martin José Marco-Contelles Fakher Chabchoub Patrick Dallemagne Christophe Rochais Krzysztof Jozwiak Lhassane Ismaili Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation Molecules Biginelli reaction multitarget-directed ligands calcium channel antagonism Nrf2 |
| title | Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation |
| title_full | Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation |
| title_fullStr | Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation |
| title_full_unstemmed | Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation |
| title_short | Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation |
| title_sort | biginelli reaction synthesis of novel multitarget directed ligands with ca sup 2 sup channel blocking ability cholinesterase inhibition antioxidant capacity and nrf2 activation |
| topic | Biginelli reaction multitarget-directed ligands calcium channel antagonism Nrf2 |
| url | https://www.mdpi.com/1420-3049/28/1/71 |
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