title: Novel benzylidenephenylpyrrolizinones with pleiotropic activities potentially useful in Alzheimer's disease treatment.
abstract: This work describes the synthesis and the biological evaluation of novel benzylidenephenylpyrrolizinones as potential antioxidant, metal chelating or amyloid β (βA) aggregation inhibitors. Some derivatives exhibited interesting results in regard to several of the performed evaluations and appear as valuable Multi-Target Directed Ligands with potential therapeutic interest in Alzheimer's disease. Among them, compound 29 particularly appears as a valuable radical and NO scavenger, a Cu(II) and Fe(II) chelating agent and exhibits moderate βA aggregation inhibition properties. These activities, associated to a good predictive bioavailability and a lack of cytotoxicity, design it as a promising hit for further in vivo investigation.
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Jourdan
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Since
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Laïla
authors.initials: L
authors.lastname: El Kihel
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Lecoutey
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Corvaisier
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Legay
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Jana
authors.initials: J
authors.lastname: Sopkova-de Oliveira Santos
authors.affiliation: CIBLOT, IPSIT - IFR14, 5 rue Jean Baptiste Clément, 92290 Chatenay-Malabry, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Malzert-Fréon
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France. Electronic address: christophe.rochais@unicaen.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.affiliation: Normandie Université, UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), F-14032 Caen, France. Electronic address: patrick.dallemagne@unicaen.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007624:KB Cells; D008958:Models, Molecular; D015394:Molecular Structure; D066329:Protein Aggregates / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001593:Benzyl Compounds; D066329:Protein Aggregates; D011758:Pyrroles
keywords: Alzheimer; Anti βA aggregation; Antichelating; Antioxidant; MTDL; Pleiotrope; Pyrrolizinone