title: Natural cholinesterase inhibitors from Myristica cinnamomea King.
abstract: A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84±0.19 and 1.76±0.21μM, respectively) and 4 (1.94±0.27 and 2.80±0.49μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver-Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Siti Mariam
authors.initials: SM
authors.lastname: Abdul Wahab
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Sivasothy
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Products and Drug Research (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sook Yee
authors.initials: SY
authors.lastname: Liew
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, University Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Jamaludin
authors.initials: J
authors.lastname: Mohamad
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Products and Drug Research (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: khalijah@um.edu.my.
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D026324:Myristicaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase enzyme; Acylphenols; Butyrylcholinesterase enzyme; Dimeric acylphenols; Malabaricone E; Myristica cinnamomea King; Myristicaceae