Molecules
(Dec 2022)
Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca<sup>2+</sup> Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation
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
Affiliations
Rim Malek
Laboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France
Alexey Simakov
PEPITE EA4267, University Franche-Comté, F-25000 Besançon, France
Audrey Davis
Centre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France
Maciej Maj
Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland
Paul J. Bernard
Laboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France
Artur Wnorowski
Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland
Helene Martin
PEPITE EA4267, University Franche-Comté, F-25000 Besançon, France
José Marco-Contelles
Laboratory of Medicinal Chemistry (IQOG, CSIC), C/ Juan de la Cierva 3, 28006 Madrid, Spain
Fakher Chabchoub
Laboratory of Applied Chemistry: Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, Sfax 3000, Tunisia
Patrick Dallemagne
Centre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France
Christophe Rochais
Centre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie University, Unicaen, CERMN, 14000 Caen, France
Krzysztof Jozwiak
Department of Biopharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093 Lublin, Poland
Lhassane Ismaili
Laboratoire LINC UR 481, Pôle de Chimie Médicinale, University Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France
DOI
https://doi.org/10.3390/molecules28010071
Journal volume & issue
Vol. 28,
no. 1
Abstract
Read online
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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