6-Hydroxy- and 6-methoxy-beta-carbolines as acetyl- and butyrylcholinesterase inhibitors.
In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on beta-carbolines (BCs). 6-Oxygenated beta-carboline and beta-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine.
Schott
Yvonne
Y
Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.
Decker
Michael
M
Rommelspacher
Hans
H
Lehmann
Jochen
J
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005702:Galantamine / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D048448:Phenylcarbamates / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D000068836:Rivastigmine; D012701:Serotonin / Q000378:metabolism
D002243:Carbolines; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D005702:Galantamine; D012701:Serotonin; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine