Synthesis of Imperatorin Analogs and Their Evaluation as Acetylcholinesterase and Butyrylcholinesterase Inhibitors

• Published in: Archiv der Pharmazie (Weinheim) Vol. 346; no. 11; pp. 775 - 782
• Main Authors: Granica, Sebastian, Kiss, Anna K., Jarończyk, Małgorzata, Maurin, Jan K., Mazurek, Aleksander P., Czarnocki, Zbigniew
• Format: Journal Article
• Language: English; German
• Published: WEINHEIM Blackwell Publishing Ltd 01.11.2013; Wiley; Wiley Subscription Services, Inc
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Alzheimer's disease; Angelica archangelica; Animals; Binding Sites; Butyrylcholinesterase; Butyrylcholinesterase - metabolism; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - pharmacology; Furocoumarins; Furocoumarins - chemical synthesis; Furocoumarins - pharmacology; Galantamine - pharmacology; Life Sciences & Biomedicine; Molecular Docking Simulation; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; ANGELICA-DAHURICA; COMPONENTS; Angelica archangelica; Acetylcholinesterase; Butyrylcholinesterase; COUMARINS; PSORALEN; SUBSTRATE; ROOTS; Alzheimer's disease; DERIVATIVES; Furocoumarins; FURANOCOUMARINS; CONSTITUENTS
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201300259

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. Several imperatorin analogs were synthesized using imperatorin and xanthotoxin as substrates. Their anti‐cholinesterase activities were evaluated, and all active compounds showed selectivity toward butyrylcholinesterase (BuChE) rather than acetylcholinesterase. The most active compounds were 8‐(3‐methylbutoxy)‐psoralen and 8‐hexoxypsoralen with IC50 values for BuChE of around 16.5 and 16.4 µM, respectively.