Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-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 m...

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Autores principales: Malek, Rim, Simakov, Alexey, Davis, Audrey, Maj, Maciej, Bernard, Paul J., Wnorowski, Artur, Martin, Helene, Marco-Contelles, José, Chabchoub, Fakher, Dallemagne, Patrick, Rochais, Christophe, Jozwiak, Krzysztof, Ismaili, Lhassane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822022/
https://www.ncbi.nlm.nih.gov/pubmed/36615267
http://dx.doi.org/10.3390/molecules28010071
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author Malek, Rim
Simakov, Alexey
Davis, Audrey
Maj, Maciej
Bernard, Paul J.
Wnorowski, Artur
Martin, Helene
Marco-Contelles, José
Chabchoub, Fakher
Dallemagne, Patrick
Rochais, Christophe
Jozwiak, Krzysztof
Ismaili, Lhassane
author_facet Malek, Rim
Simakov, Alexey
Davis, Audrey
Maj, Maciej
Bernard, Paul J.
Wnorowski, Artur
Martin, Helene
Marco-Contelles, José
Chabchoub, Fakher
Dallemagne, Patrick
Rochais, Christophe
Jozwiak, Krzysztof
Ismaili, Lhassane
author_sort Malek, Rim
collection PubMed
description Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-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.
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spelling pubmed-98220222023-01-07 Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation Malek, Rim Simakov, Alexey Davis, Audrey Maj, Maciej Bernard, Paul J. Wnorowski, Artur Martin, Helene Marco-Contelles, José Chabchoub, Fakher Dallemagne, Patrick Rochais, Christophe Jozwiak, Krzysztof Ismaili, Lhassane Molecules Article Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-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. MDPI 2022-12-22 /pmc/articles/PMC9822022/ /pubmed/36615267 http://dx.doi.org/10.3390/molecules28010071 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Malek, Rim
Simakov, Alexey
Davis, Audrey
Maj, Maciej
Bernard, Paul J.
Wnorowski, Artur
Martin, Helene
Marco-Contelles, José
Chabchoub, Fakher
Dallemagne, Patrick
Rochais, Christophe
Jozwiak, Krzysztof
Ismaili, Lhassane
Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title_full Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title_fullStr Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title_full_unstemmed Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title_short Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca(2+) Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
title_sort biginelli reaction synthesis of novel multitarget-directed ligands with ca(2+) channel blocking ability, cholinesterase inhibition, antioxidant capacity, and nrf2 activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822022/
https://www.ncbi.nlm.nih.gov/pubmed/36615267
http://dx.doi.org/10.3390/molecules28010071
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