Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A
A new quaternary β-carboline alkaloid, nostocarboline (I), 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. I is a potent butyrylcholinesterase (BChE) inhibitor, with an IC50 of 13.2 μM. The related 2-methylnorharmane, which is present in the human brain and might be relevant to Parkinson's disease, was also detected to be a BChE inhibitor (11.2 μM). These inhibitory concentrations are comparable to galanthamine, an approved drug for the treatment of Alzheimer's disease. I can thus be considered as a lead for the development of novel neurochemicals.