Molecules (May 2016)
Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer’s Disease
- Youssef Dgachi,
- Oscar M. Bautista-Aguilera,
- Mohamed Benchekroun,
- Hélène Martin,
- Alexandre Bonet,
- Damijan Knez,
- Justyna Godyń,
- Barbara Malawska,
- Stanislav Gobec,
- Mourad Chioua,
- Jana Janockova,
- Ondrej Soukup,
- Fakher Chabchoub,
- José Marco-Contelles,
- Lhassane Ismaili
Affiliations
- Youssef Dgachi
- Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B.P. 802, Sfax 3000, Tunisia
- Oscar M. Bautista-Aguilera
- Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques, EA 481, UFR SMP, Univ. Franche-Comté, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon F-25000, France
- Mohamed Benchekroun
- Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques, EA 481, UFR SMP, Univ. Franche-Comté, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon F-25000, France
- Hélène Martin
- Laboratory of Cell Toxicology, EA 4267, University of Bourgogne Franche-Comté, 19 rue Ambroise Paré, Besançon Cedex 25030, France
- Alexandre Bonet
- Laboratory of Cell Toxicology, EA 4267, University of Bourgogne Franche-Comté, 19 rue Ambroise Paré, Besançon Cedex 25030, France
- Damijan Knez
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia
- Justyna Godyń
- Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9 Street, Krakow 30-688, Poland
- Barbara Malawska
- Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9 Street, Krakow 30-688, Poland
- Stanislav Gobec
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia
- Mourad Chioua
- Laboratory of Medicinal Chemistry (IQOG, CSIC) C/Juan de la Cierva 3, Madrid 28006, Spain
- Jana Janockova
- Biomedical Research Center, University Hospital Hradec Kralove, 500 05 Hradec Králove, Czech Republic
- Ondrej Soukup
- Biomedical Research Center, University Hospital Hradec Kralove, 500 05 Hradec Králove, Czech Republic
- Fakher Chabchoub
- Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B.P. 802, Sfax 3000, Tunisia
- José Marco-Contelles
- Laboratory of Medicinal Chemistry (IQOG, CSIC) C/Juan de la Cierva 3, Madrid 28006, Spain
- Lhassane Ismaili
- Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques, EA 481, UFR SMP, Univ. Franche-Comté, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon F-25000, France
- DOI
- https://doi.org/10.3390/molecules21050634
- Journal volume & issue
-
Vol. 21,
no. 5
p. 634
Abstract
We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.
Keywords
- Alzheimer’s disease
- quinazolinones
- multicomponent reactions
- multitarget-directed ligands
- antioxidants
- cholinesterase inhibitors
- hepatotoxicity
