title: Multifunctional diamine AGE/ALE inhibitors with potential therapeutical properties against Alzheimer's disease.
abstract: An important part of pathogenesis of Alzheimer's disease (AD) is attributed to the contribution of AGE (Advanced Glycation Endproducts) and ALE (Advanced Lipid peroxidation Endproducts). In order to attenuate the progression of AD, we designed a new type of molecules that consist of two trapping parts for reactive carbonyl species (RCS) and reactive oxygen species (ROS), precursors of AGE and ALE, respectively. These molecules also chelate transition metals, the promoters of ROS formation. In this paper, synthesis of the new AGE/ALE inhibitors and evaluation of their physicochemical and biological properties (carbonyl trapping capacity, antioxidant activity, Cu(2+)-chelating capacity, cytotoxicity and protective effect against in vitro MGO-induced apoptosis in the model AD cell-line PC12) are described. It is found that compounds 40b and 51e possess promising therapeutic potentials for treating AD.
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie des Antimicrobiens et des Agroressouces, LG2A, UMR CNRS 7378, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 01, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Lohou
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie des Antimicrobiens et des Agroressouces, LG2A, UMR CNRS 7378, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 01, France. Electronic address: andre.sasaki@u-picardie.fr.
authors.forename: N André
authors.initials: NA
authors.lastname: Sasaki
authors.affiliation: Université de Picardie Jules Verne, UFR de Médecine, 1 Rue des Louvels, F-80037, Amiens Cedex 01, France; INSERM U1088, Centre Universitaire de Recherche en Santé (CURS), Avenue René Laënnec - Salouel, F-80054, Amiens Cedex 01, France; CHU Amiens Picardie, Avenue René Laënnec - Salouel, F-80054, Amiens Cedex 01, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Boullier
authors.affiliation: Université de Picardie Jules Verne, Laboratoire de Glycochimie des Antimicrobiens et des Agroressouces, LG2A, UMR CNRS 7378, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 01, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D016716:PC12 Cells; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003959:Diamines; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D011765:Pyruvaldehyde; D003300:Copper
keywords: AGE (Advanced Glycation Endproducts); ALE (Advanced Lipid peroxidation Endproducts); Alzheimer's disease; Biometal dyshomeostasis; Carbonyl stress; Diamine building blocks; Hydroxypyridinone (HOPO) ligands; Oxidative stress; Phenolic acids