title: Synthesis and biological activity of derivatives of tetrahydroacridine as acetylcholinesterase inhibitors.
abstract: Current state of medical sciences does not allow to treatment neurodegenerative diseases such as Alzheimer's disease (AD). At present treatment of AD is severely restricted. The main class of medicines which are applied in AD is acetylcholinesterase inhibitors (AChEIs) like tacrine, donepezil, galantamine and rivastigmine that do not contribute to significant and long-term improvement in cognitive and behavioural functions. In this work, we report synthesis and biological evaluation of new hybrids of tacrine-6-hydrazinonicotinamide. The synthesis was based on the condensation reaction between tacrine derivatives and the hydrazine nicotinate moiety (HYNIC). All obtained compounds present affinity for both cholinesterases and are characterized by high selectivity in relation to butyrylcholinesterase (BChE).
authors.affiliation: Department Pharmaceutical Chemistry and Drug Analyses, Medical University, ul. Muszyńskiego 1, 90-151 Lodz, Poland. pawel.szymanski@umed.lodz.pl
authors.forename: Paweł
authors.initials: P
authors.lastname: Szymański
authors.forename: Magdalena
authors.initials: M
authors.lastname: Markowicz
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Mikiciuk-Olasik
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D009525:Niacin / Q000737:chemistry; D013619:Tacrine / Q000737:chemistry
chemical_list: D000166:Acridines; D002800:Cholinesterase Inhibitors; D009525:Niacin; D013619:Tacrine; D000110:Acetylcholinesterase