Nostocarboline:: Isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A

A new quaternary beta-carboline alkaloid, nostocarboline (1), 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 (1) was found to be a potent butyrylcholinesterase (BChE) inhibitor, with an IC50 of 13.2 mu M. 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 mu M). These inhibitory concentrations are comparable to galanthamine, an approved drug for the treatment of Alzheimer's disease (AID). Nostocarboline (1) can thus be considered as a lead for the development of novel neurochemicals.