Planta Med 2012; 78 - PD35
DOI: 10.1055/s-0032-1320393

Synthesis of imperatorin analogoues and their evaluation as acetylcholinestarase and butyrylcholinesterase inhibitors

S Granica 1, 2, AK Kiss 1, Z Czarnocki 2
  • 1Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, 02–097 Warsaw, Poland
  • 2Faculty of Chemistry, University of Warsaw, Pasteura 1, 02–093 Warsaw

In this study we analyzed inhibitory activity of some synthesized furocoumarins towards acetyl- and butyrylcholinesterase. We used fruits of Archangelica angelica L. obtained after cultivation for medical purposes, as a source of imperatorin and other linear furocoumarins. Apart from isolated imperatorin we used commercially available xanthotoxin as a substrate for chemical transformations leading to several derivatives differing in the structure of a side chain of furocoumarin rings. Anti-cholinesterase activity was evaluated in in vitro experiments according to the modified Ellman's method using 96-well plate reader. For each of synthesized compounds IC50 value for both enzymes was established basing on concentration inhibition curves. Galantamine hydrobromide was used as a positive control in enzymatic experiments. All active compounds showed significant selectivity towards butyrylcholinesterase rather than acetylcholinesterase. The most active were 8-(3-methylbutoxy)-psoralen and 8-hexoxypsolaren with IC50 for BuChE around 16.5 and 16.4µM respectively. The results of our study may be considered as the beginning of a search for potential anti-Alzheimer's disease drugs based on the structure of natural furocoumarins.