title: Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis.
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.
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Sook Yee
authors: SY
authors: Liew
authors: Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
authors: Kooi Yeong
authors: KY
authors: Khaw
authors: Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
authors: Vikneswaran
authors: V
authors: Murugaiyah
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Chung Yeng
authors: CY
authors: Looi
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Yi Li
authors: YL
authors: Wong
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Mohd Rais
authors: MR
authors: Mustafa
authors: Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, Cedex, France.
authors: Marc
authors: M
authors: Litaudon
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia . Electronic address: khalijah@um.edu.my.
authors: Khalijah
authors: K
authors: Awang
mesh_terms: D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D024301:Plant Bark / Q000737:chemistry; D019666:Rubiaceae / Q000737:chemistry*; D046948:Secologanin Tryptamine Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D046948:Secologanin Tryptamine Alkaloids; D002091:Butyrylcholinesterase
keywords: Angustidine; Cholinesterase; Kinetic study; Molecular docking; Nauclea officinalis