Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads. (August 2021)

• Record Type: Journal Article
• Authors: Orhan, Ilkay Erdogan; Tosun, Fatma; Senol Deniz, Fatma Sezer; Eren, Gokcen; Mıhoğlugil, Feyyaz; Akalgan, Demet; Miski, Mahmut
• Is Part Of: Phytochemistry letters. Volume 44(2021)
• Page Start: 48
• Page End: 54
• Publication Date: 2021-08
• Subjects: Coumarin -- Alzheimer's disease -- Cholinesterase -- Tyrosinase -- Molecular docking; Botanical chemistry -- Periodicals; Chimie végétale -- Périodiques; 572.205
• DOI: 10.1016/j.phytol.2021.05.001
• Languages: English
• ISSNs: 1874-3900

Abstract

Graphical abstract: Highlights: Seventeen natural coumarins were tested against cholinesterases and tyrosinase. 14′-Acetoxybadrakemin, colladonin, karatavicinol, and isoimperatorin show high BChE inhibitor activity. The active coumarins interact with the oxyanion hole and the peripheral anionic site of ChEs. None of the coumarins were able to inhibit tyrosinase effectively. 14′-Acetoxybadrakemin, colladonin, karatavicinol, and isoimperatorin are the lead candidates. Abstract: Seventeen natural coumarin derivatives; badrakemin (1 ), 14′-acetoxybadrakemin (2 ), badrakemone (3 ), 14′-acetoxybadrakemone (4 ), colladonin (5 ), colladonin acetate (6 ), 14′-acetoxycolladonin (7 ), karatavicinol (8 ), deltoin (9 ), smyrnioridin (10 ), marmesin (11 ), osthol (12 ), oxypeucedanin (13 ), oxypeucedanin hydrate (14 ), isoimperatorin (15 ), scopoletin (16 ), and umbelliprenin (17 ), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer's disease as well as tyrosinase (TYR) as the target for Parkinson's disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15 ) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15 ) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates.