title: Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy.
abstract: Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 ± 1.7 μM), and a very potent antioxidant agent on the basis of the ORAC test (2.31 ± 0.29 μmol·Trolox/μmol compound).
authors.affiliation: Equipe de Synthèse de Molécules à Objectif Thérapeutique, Laboratoire des Produits Naturels d'Origine Végétale et de Synthèse Organique (PHYSYNOR), Université des frères Mentouri, Campus de Chaabat-Ersas, Constantine 25000, Algeria. boulebdhoussam@hotmail.fr.
authors.forename: Houssem
authors.initials: H
authors.lastname: Boulebd
authors.affiliation: 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, F-Besançon 25000, France. lhassane.ismaili@univ-fcomte.fr.
authors.forename: Lhassane
authors.initials: L
authors.lastname: Ismaili
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, Bologna 40126, Italy. manuela.bartolini3@unibo.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.affiliation: Equipe de Synthèse de Molécules à Objectif Thérapeutique, Laboratoire des Produits Naturels d'Origine Végétale et de Synthèse Organique (PHYSYNOR), Université des frères Mentouri, Campus de Chaabat-Ersas, Constantine 25000, Algeria. bouraiou.abdelmalek@yahoo.fr.
authors.forename: Abdelmalek
authors.initials: A
authors.lastname: Bouraiou
authors.affiliation: Department for Life Quality Studies, University of Bologna, Corso d'Augusto, 237, Rimini 47921, Italy. vincenza.andrisano@unibo.it.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.affiliation: Laboratoire de Toxicologie Cellulaire, EA 4267, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon Cedex 25030, France. helene.martin@univ-fcomte.fr.
authors.forename: Helene
authors.initials: H
authors.lastname: Martin
authors.affiliation: Laboratoire de Toxicologie Cellulaire, EA 4267, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon Cedex 25030, France. alexandre.bonet@univ-fcomte.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bonet
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, Ctra. Barcelona, Km. 33.5, Alcalá de Henares 28817, Spain. ignacio.moraleda@uah.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moraleda
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, Ctra. Barcelona, Km. 33.5, Alcalá de Henares 28817, Spain. isabel.iriepa@uah.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Iriepa
authors.affiliation: Laboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. mchioua@gmail.com.
authors.forename: Mourad
authors.initials: M
authors.lastname: Chioua
authors.affiliation: Equipe de Synthèse de Molécules à Objectif Thérapeutique, Laboratoire des Produits Naturels d'Origine Végétale et de Synthèse Organique (PHYSYNOR), Université des frères Mentouri, Campus de Chaabat-Ersas, Constantine 25000, Algeria. abelbelfaitah@yahoo.fr.
authors.forename: Ali
authors.initials: A
authors.lastname: Belfaitah
authors.affiliation: Laboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. iqoc21@iqog.csic.es.
authors.forename: José
authors.initials: J
authors.lastname: Marco-Contelles
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D008099:Liver / Q000187:drug effects; D000072257:Oxygen Radical Absorbance Capacity; D013619:Tacrine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D013619:Tacrine
keywords: Alzheimer′s disease; ORAC; antioxidant activity; cholinesterase inhibitors; hepatotoxicity; tacrine analogues