A compound isolated from the cyanobacterium Nostoc has revealed itself as a promising candidate for staving off the devastating symptoms of Alzheimer's disease (AD), according to laboratory studies by researchers in Switzerland.

Karl Gademann

Friedrich Jüttner's group at the Limnological Station of the University of Zürich have for many years studied chemical interactions in freshwater ecosystems. "Cyanobacteria are a prominent group from which we have isolated and characterized several new compounds," he told Reactive Reports. "We were interested in the insecticidal activities of cyanobacteria as they often flourish on stones and walls of streams and on lake shores, and are digested by insect larvae." With this in mind, the team developed an assay for inhibitors of cholinesterase (a target enzyme for insecticides) and found that nostocarboline was as active as the Alzheimer's drug, galanthamine.

However, to learn more about this compound, NMR analysis was needed and that requires milligram quantities. "At the Limnological Station we have facilities for mass cultivation of cyanobacteria," explains Jüttner, "and we produced 100 g amounts of Nostoc 78-12A." The cyanobacterium had been isolated by P. Wolk, of MSU, East Lancing (from a canal). Jüttner's team extracted the biomass with 60% aqueous methanol to obtain a bioactive solution that contained a large number of different compounds.

"The trick to obtaining an enriched fraction of nostocarboline was to remove the solvent and to extract the dry residue with 95% acetonitrile," adds Jüttner. The nostocarboline was mostly dissolved and the majority of the other compounds remained undissolved. This extract was then extensively purified by HPLC to give about 1 milligram of pure compound.

Jüttner then sent the sample to Karl Gademann of the Swiss Federal Institute of Technology (ETH) in Zurich and colleagues for structural elucidation by NMR spectrometry and total synthesis.

As well as being an insect target, cholinesterase is crucial in the human brain for memory formation and thinking. Its breakdown is associated with progression of Alzheimer's disease. Given its comparable potency to the drug galanthamine as a cholinesterase inhibitor, nostocarboline could provide drug researchers with a new lead in the fight against this debilitating disease, although full testing will take several years.

J Nat Prod, 2005, 68, 1793-1795; http://dx.doi.org/10.1021/np050312l

http://www.research-projects.unizh.ch/a349.htm

http://www.gademann.ethz.ch/people/karl

http://www.prl.msu.edu/wolk.shtml