Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads
Yükleniyor...
Dosyalar
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 ?M, 29.2 ?M, 37.2 ?M, and 50.1 ?M, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 ?M) at 100 ?g/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 ?g/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates.
Açıklama
Anahtar Kelimeler
Alzheimer's Disease, Cholinesterase, Coumarin, Molecular Docking, Tyrosinase
Kaynak
Phytochemistry Letters
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
44
Sayı
Künye
Orhan, I. E., Tosun, F., Deniz, F. S. S., Eren, G., Mıhoğlugil, F., Akalgan, D., & Miski, M. (2021). Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads. Phytochemistry Letters, 44, 48-54.
