Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A.
A new quaternary beta-carboline alkaloid, nostocarboline, was isolated from the freshwater cyanobacterium Nostoc 78-12A, and its constitution was assigned by 2D-NMR methods. The structure was proven by its total synthesis starting from norharmane via chlorination at C-6 and methylation at N-2. Nostocarboline was found to be a potent butyrylcholinesterase (BChE) inhibitor, with an IC(50) of 13.2 microM. The related 2-methylnorharmane, which is present in the human brain and might be relevant to Parkinson's disease (PD), was also determined to be a BChE inhibitor (11.2 microM). These inhibitory concentrations are comparable to galanthamine, an approved drug for the treatment of Alzheimer's disease (AD). Nostocarboline can thus be considered as a lead for the development of novel neurochemicals.
Becher
Paul G
PG
Limnological Station, Institute of Plant Biology, University of Zürich, Seestrasse 187, 8802 Kilchberg, Switzerland.
Beuchat
Julien
J
Gademann
Karl
K
Jüttner
Friedrich
F
D001921:Brain / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002243:Carbolines; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005702:Galantamine / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D046937:Nostoc / Q000737:chemistry*; D010300:Parkinson Disease / Q000188:drug therapy
D002243:Carbolines; D002800:Cholinesterase Inhibitors; C507037:nostocarboline; D005702:Galantamine; D002091:Butyrylcholinesterase