Natural cholinesterase inhibitors from Myristica cinnamomea King

Document Type

Article

Publication Date

1-1-2016

Abstract

A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2–4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84 ± 0.19 and 1.76 ± 0.21 μM, respectively) and 4 (1.94 ± 0.27 and 2.80 ± 0.49 μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver–Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole.

Keywords

Myristica cinnamomea King, Myristicaceae, Acylphenols, Dimeric acylphenols, Malabaricone E, Acetylcholinesterase enzyme, Butyrylcholinesterase enzyme

Divisions

CHEMISTRY

Funders

University of Malaya Research Grant RP001-2012A/B ,Centre National de la Recherche Scientifique (CNRS) grant (57-02-03-1007)

Publication Title

Bioorganic & Medicinal Chemistry Letters

Volume

26

Issue

15

Publisher

Elsevier

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