TY - JOUR
T1 - Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis
AU - Liew, Sook Yee
AU - Khaw, Kooi Yeong
AU - Murugaiyah, Vikneswaran
AU - Looi, Chung Yeng
AU - Wong, Yi Li
AU - Mustafa, Mohd Rais
AU - Litaudon, Marc
AU - Awang, Khalijah
N1 - Funding Information:
This work was supported by University of Malaya research grants (UM.C/625/1/HIR/MOHE/SC/37 and PV050/2012A) and Centre National de la Recherche Scientifique (CNRS) grant (57-02-03-1007). The authors thank D.M. Nor and R. Syamsir for collection of plant material and T. L. Eng for botanical identification. The plant collection was carried out within the framework of an official agreement between the CNRS and the University of Malaya (Malaysia).
Publisher Copyright:
© 2014 Elsevier GmbH.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/8/9
Y1 - 2015/8/9
N2 - Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.
AB - Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.
KW - Angustidine
KW - Cholinesterase
KW - Kinetic study
KW - Molecular docking
KW - Nauclea officinalis
UR - http://www.scopus.com/inward/record.url?scp=84915746452&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2014.11.003
DO - 10.1016/j.phymed.2014.11.003
M3 - Article
C2 - 25636869
AN - SCOPUS:84915746452
VL - 22
SP - 45
EP - 48
JO - Phytomedicine : international journal of phytotherapy and phytopharmacology
JF - Phytomedicine : international journal of phytotherapy and phytopharmacology
SN - 0944-7113
IS - 1
ER -