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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-12, Vol.28 (1)
Main Authors: 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
Format: Article
Language:English
Subjects:
Alzheimer Disease - drug therapy
Antioxidants - chemical synthesis
Calcium Channel Blockers - chemical synthesis
Cholinesterase Inhibitors - chemical synthesis
Humans
Ligands
Molecular Targeted Therapy
NF-E2-Related Factor 2 - metabolism
Structure-Activity Relationship
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Summary: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.
ISSN:1420-3049