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Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca²⁺ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation.

ABSTRACT: 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.

SUBMITTER: Malek R

PROVIDER: S-EPMC9822022 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation.

Malek Rim R Simakov Alexey A Davis Audrey A Maj Maciej M Bernard Paul J PJ Wnorowski Artur A Martin Helene H Marco-Contelles José J Chabchoub Fakher F Dallemagne Patrick P Rochais Christophe C Jozwiak Krzysztof K Ismaili Lhassane L

Molecules (Basel, Switzerland) 20221222 1

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 comp ...[more]

PMID: 36615267

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