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Bioorg Med Chem Lett. 2016 Aug 1;26(15):3785-92. doi: 10.1016/j.bmcl.2016.05.046. Epub 2016 May 17.

Natural cholinesterase inhibitors from Myristica cinnamomea King.

Author information

1
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
2
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Products and Drug Research (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia.
3
Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, University Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
4
Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
5
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Products and Drug Research (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: khalijah@um.edu.my.

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±0.21μM, respectively) and 4 (1.94±0.27 and 2.80±0.49μM, 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:

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

PMID:
27236720
DOI:
10.1016/j.bmcl.2016.05.046
[Indexed for MEDLINE]

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