title: Quinolone-benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer disease.
abstract: Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds show effective AchE inhibitions, high selectivities over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of quinolone derivatives to serve in the design of N-benzylpiperidine linked multipotent molecules for the treatment of Alzheimer Disease has been established.
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France. Electronic address: marc.pudlo@univ-fcomte.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Pudlo
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Luzet
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
authors.forename: Lhassane
authors.initials: L
authors.lastname: Ismaïli
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tomassoli
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Iutzeler
authors.affiliation: Nanomedicine Lab, EA-4662, UFR SMP, 19 rue Ambroise Paré Université de Franche Comté, 25030 Besançon Cedex, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Refouvelet
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000737:chemistry* / Q000627:therapeutic use; D015363:Quinolones / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D010880:Piperidines; D015363:Quinolones; C071293:1-benzylpiperidine; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Antioxidant; Hybrid; N-Benzylpiperidine; Quinolone