Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis

Sook Yee Liew; Kooi Yeong Khaw; Vikneswaran Murugaiyah; Chung Yeng Looi; Yi Li Wong; Mohd Rais Mustafa; Marc Litaudon; Khalijah Awang

doi:10.1016/j.phymed.2014.11.003

Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis

Phytomedicine. 2015 Jan 15;22(1):45-8. doi: 10.1016/j.phymed.2014.11.003. Epub 2014 Nov 20.

Authors

Sook Yee Liew¹, Kooi Yeong Khaw², Vikneswaran Murugaiyah², Chung Yeng Looi³, Yi Li Wong³, Mohd Rais Mustafa³, Marc Litaudon⁴, Khalijah Awang⁵

Affiliations

¹ Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
² Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
³ Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
⁴ Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, Cedex, France.
⁵ Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia . Electronic address: khalijah@um.edu.my.

PMID: 25636869
DOI: 10.1016/j.phymed.2014.11.003

Abstract

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.

Keywords: Angustidine; Cholinesterase; Kinetic study; Molecular docking; Nauclea officinalis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / isolation & purification
Cholinesterase Inhibitors / pharmacology*
Inhibitory Concentration 50
Plant Bark / chemistry
Rubiaceae / chemistry*
Secologanin Tryptamine Alkaloids / isolation & purification
Secologanin Tryptamine Alkaloids / pharmacology*

Substances

Cholinesterase Inhibitors
Secologanin Tryptamine Alkaloids
Butyrylcholinesterase