title: Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment.
abstract: A new group of compounds, promising for the design of original multitarget therapeutic agents for treating neurodegenerative diseases, based on conjugates of aminoadamantane and carbazole derivatives was synthesized and investigated. Compounds of these series were found to interact with a group of targets that play an important role in the development of this type of diseases. First of all, these compounds selectively inhibit butyrylcholinesterase, block NMDA receptors containing NR2B subunits while maintaining the properties of MK-801 binding site blockers, exert microtubules stabilizing properties, and possess the ability to protect nerve cells from death at the calcium overload conditions. The leading compound C-2h has been shown the most promising effects on all analyzed parameters. Thus, these compounds can be regarded as promising candidates for the design of multi-target disease-modifying drugs for treatment of AD and/or similar neuropathologies.
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Sergey O
authors.initials: SO
authors.lastname: Bachurin
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Shevtsova
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Galina F
authors.initials: GF
authors.lastname: Makhaeva
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Grigoriev
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Boltneva
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Kovaleva
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.|Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia.
authors.forename: Sofya V
authors.initials: SV
authors.lastname: Lushchekina
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Pavel N
authors.initials: PN
authors.lastname: Shevtsov
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Margarita E
authors.initials: ME
authors.lastname: Neganova
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Redkozubova
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Bovina
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Gabrelyan
authors.affiliation: Department of Pharmacology, Therapeutic Faculty, I. M. Setchenov Moscow Medical Academy, ul. Bol'shaya Pirogovskaya 2/6, Moscow, 119881 Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Fisenko
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Sokolov
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Aksinenko
authors.affiliation: Universidad San Sebastián, General Cruz 1577, Concepción, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.|Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile.
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
authors.affiliation: Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.|GALLY International Biomedical Research Consulting LLC., San Antonio, TX 78229, USA.|School of Health Science and Healthcare Administration, University of Atlanta, Johns Creek, GA 30097, USA.
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000547:Amantadine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D043182:Carboxylesterase / Q000037:antagonists & inhibitors; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008559:Memantine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D062105:Molecular Docking Simulation; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D002227:Carbazoles; D002800:Cholinesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; C041514:carbazole; D000547:Amantadine; D043182:Carboxylesterase; D008559:Memantine