title: Acetylcholinesterase inhibitory activity and molecular docking study of steroidal alkaloids from Holarrhena pubescens barks.
abstract: An alkaloidal extract of the bark of Holarrhena pubescens showed several inhibition zones of acetylcholinesterase (AChE) inhibitor, using a bioautographic assay. Activity-guided fractionation afforded three new steroidal alkaloids, mokluangins A-C (1-3), together with three known compounds, antidysentericine (4), holaphyllamine (5), methylholaphyllamine (6). All structures were elucidated by analysis of NMR and MS spectroscopic data. Compound 2 showed moderate antibacterial activity against Bacillus subtilis and Escherichia coli with the MIC value of 16 μg/mL, while compound 3 exhibited moderate selective activity against E. coli with the MIC value of 16 μg/mL. In addition, compounds 1-4 also showed strong AChE inhibiting activity with IC50 values ranging from 1.44 to 23.22 μM. Molecular docking calculations were also performed and the results demonstrated that all compounds can bind at the aromatic gorge of AChE with estimated binding free energies correlated well with the in vitro inhibitory profiles. Hydrophobic and hydrogen bonding interactions contribute mainly to the binding of the alkaloids where the substituents at C-3 serving as key functional groups for the AChE inhibition. Our results will allow the development of new AChE-inhibitors based on steroidal alkaloid skeleton bearing the cyclic amide moiety.
authors: Division of Chemistry, School of Science, University of Phayao, Maeka, Muang, Phayao 56000, Thailand. Electronic address: sarot.ch@up.ac.th.
authors: Sarot
authors: S
authors: Cheenpracha
authors: Division of Chemistry, School of Science, University of Phayao, Maeka, Muang, Phayao 56000, Thailand.
authors: Jitrayut
authors: J
authors: Jitonnom
authors: Division of Chemistry, School of Science, University of Phayao, Maeka, Muang, Phayao 56000, Thailand.
authors: Manutchaya
authors: M
authors: Komek
authors: Department of Chemistry, Faculty of Science, Chiang Mai University, Sutep, Muang, Chiang Mai 50200, Thailand.
authors: Thunwadee
authors: T
authors: Ritthiwigrom
authors: Natural Products Research Laboratory, School of Science, Mae Fah Luang University, Tasud, Muang, Chiang Rai 57100, Thailand.
authors: Surat
authors: S
authors: Laphookhieo
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000470:Alkaloids / Q000737:chemistry*; D001412:Bacillus subtilis / Q000201:enzymology; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D035462:Holarrhena / Q000737:chemistry*; D062105:Molecular Docking Simulation; D024301:Plant Bark / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D013256:Steroids; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase inhibitor; Antibacterial activity; Holarrhena pubescens; Mokluangins A–C; Molecular docking; Steroidal alkaloids