title: Cholinesterase inhibitory activity of isoquinoline alkaloids from three Cryptocarya species (Lauraceae).
abstract: Alzheimer's disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer's disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (-)-desmethylsecoantofine 2, (+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC50 value of 3.95μM. Analysis of the Lineweaver-Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72μM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: Wan Nurul Nazneem
authors: WNN
authors: Wan Othman
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Products and Drug Discovery (CENAR), 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: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, University Paris-Saclay, 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; Centre for Natural Products and Drug Discovery (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: khalijah@um.edu.my.
authors: Khalijah
authors: K
authors: Awang
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D031369:Cryptocarya / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D010936:Plant Extracts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 2-Methoxyatherosperminine; Butyrylcholinesterase; Cryptocarya; Enzyme kinetic; Molecular docking; Phenanthrene