Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis

Liew SY 1 , Khaw KY 2 , Murugaiyah V 2 , Looi CY 3 , Wong YL 3 , Mustafa MR 3 Show all authors , Litaudon M 4 , Awang K 5

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
Phytomedicine, 2015 Jan 15;22(1):45-8.
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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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