title: Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and butyrylcholinesterase inhibitors.
abstract: In this study, we synthesized several imperatorin analogs using imperatorin and xanthotoxin as substrates. The anti-cholinesterase activities of all compounds were evaluated in in vitro experiments according to the modified Ellman's method. For each synthesized compound, IC50 values for both enzymes were established. Galantamine hydrobromide was used as a positive control in the enzymatic experiments. All active compounds showed selectivity toward butyrylcholinesterase (BuChE) rather than acetylcholinesterase. The most active ones were 8-(3-methylbutoxy)-psoralen and 8-hexoxypsoralen with IC50 values for BuChE of around 16.5 and 16.4 µM, 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.
authors.affiliation: Faculty of Chemistry, University of Warsaw, Warsaw, Poland; Faculty of Pharmacy, Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Granica
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kiss
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jarończyk
authors.forename: Jan K
authors.initials: JK
authors.lastname: Maurin
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Czarnocki
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D005702:Galantamine / Q000494:pharmacology; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D011564:Furocoumarins; D005702:Galantamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C031534:imperatorin
keywords: Acetylcholinesterase; Alzheimer's disease; Angelica archangelica; Butyrylcholinesterase; Furocoumarins