title: Cholinesterase enzymes inhibitors from the leaves of Rauvolfia reflexa and their molecular docking study.
abstract: Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM) and BChE (IC50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. mehranfadaie_n@yahoo.com
authors.forename: Mehran
authors.initials: M
authors.lastname: Fadaeinasab
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Yalda
authors.initials: Y
authors.lastname: Kia
authors.forename: Alireza
authors.initials: A
authors.lastname: Basiri
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000737:chemistry; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000032:analysis / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D011926:Rauwolfia / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D010936:Plant Extracts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase