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KMID : 0043320180410070753
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Archives of Pharmacal Research
2018 Volume.41 No. 7 p.753 ~ p.764
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Kinetics and molecular docking of dihydroxanthyletin-type coumarins from Angelica decursiva that inhibit cholinesterase and BACE1
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Ali Md Yousof
Seong Su-Hui
Jung Hyun-Ah
Jannat Susoma
Choi Jae-Sue
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Abstract
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In the present study, we investigated the anti-Alzheimer’s disease (AD) potential of six dihydroxanthyletin-type coumarins, 4′-hydroxy Pd?C-III (1), decursidin (2), Pd?C-I (3), 4′-methoxy Pd?C-I (4), Pd?C-II (5), and Pd?C-III (6) from Angelica decursiva by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Coumarins 1?6 exhibited dose-dependent inhibition of AChE, BChE, and BACE1. IC50 values were 1.0?4.01 μM for AChE, 5.78?13.91 μM for BChE, and 1.99?17.34 μM for BACE1. Kinetic studies revealed that 1 was noncompetitive inhibitor for AChE, while 2?6 were mixed-type inhibitors of AChE. Compounds 1, 5 and 6 had mixed-type inhibitory effects against BChE; 2 was a competitive inhibitor; and 3 and 4 were noncompetitive inhibitors. Against BACE1, compounds 1, 2, 3, 5 showed mixed-type inhibition and 4, 6 were noncompetitive inhibitors. Molecular docking simulation of the compounds demonstrated negative-binding energies indicating high proximity to the active site and tight binding to the enzyme. These data suggested that the compounds inhibited AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for AD treatment.
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KEYWORD
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Angelica decursiva, Coumarins, Cholinesterase, BACE1, Molecular docking, Enzyme kinetics
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