Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-12-01 |
Deskripsi
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.