Identification of non-alkaloid acetylcholinesterase inhibitors from Ferulago campestris (Besser) Grecescu (Apiaceae)

Inhibition of Acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer's disease. Many plant derived alkaloids (such as galantamine and rivastigmine) are known for their AChE inhibitory activity. Recently, other classes of natural compounds such as terpenoids, sesquiterpene glycosides and coumarins have been studied as new AChE inhibitors, with the aim to discover less toxic compounds compared to alkaloidal ones. The Ferulago campestris roots dichloromethane extract was used for a bioassay-guided fractionation for the search of AChE inhibitors. Three coumarin derivatives (umbelliprenin 1, coladonin 2 and coladin 3), three daucane ester derivatives (siol anisate 4, ferutinin 5 and 1-acetyl-5-angeloyl lapiferol 6), two phenol derivatives (2-epilaserine 7 and epielmanticine 8) and one polyacetylene (9-epoxyfalcarindiol 9) were isolated by the bioassay-guided approach. Their structures were characterized on the basis of spectral methods (1D and 2D NMR, and MS spectroscopy). All the isolated compounds were able to inhibit the AChE (IC(50) 1.2-0.1mM) although at higher doses if compared to galantamine (6.7 μM) measured in the same conditions. The most active compounds were the daucane derivative siol anisate 4 and the epielmanticine 8, with IC(50) of 0.172 and 0.175 mM respectively.