TY - JOUR
T1 - Natural cholinesterase inhibitors from Myristica cinnamomea King
AU - Abdul Wahab, Siti Mariam
AU - Sivasothy, Yasodha
AU - Liew, Sook Yee
AU - Litaudon, Marc
AU - Mohamad, Jamaludin
AU - Awang, Khalijah
N1 - Funding Information:
The authors acknowledge the University of Malaya Research Grant RP001-2012A/B and the Centre National de la Recherche Scientifique (CNRS) grant ( 57-02-03-1007 ) which have made this work possible. The results from this work are a collaborative effort of the International French Malaysia Natural Products Laboratory between CNRS-ICSN and University of Malaya . The authors would also like to acknowledge Mr. Abdulwali Ablat for his valuable guidance and assistance in conducting the cholinesterase enzymes inhibition assay.
Publisher Copyright:
© 2016 Elsevier Ltd
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Acetylcholinesterase enzyme
KW - Acylphenols
KW - Butyrylcholinesterase enzyme
KW - Dimeric acylphenols
KW - Malabaricone E
KW - Myristica cinnamomea King
KW - Myristicaceae
UR - http://www.scopus.com/inward/record.url?scp=84969627241&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.05.046
DO - 10.1016/j.bmcl.2016.05.046
M3 - Article
C2 - 27236720
AN - SCOPUS:84969627241
VL - 26
SP - 3785
EP - 3792
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 15
ER -