Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre

Research output: Contribution to journalJournal articlepeer-review

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Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre. / Halldórsdóttir, Elsa Steinunn; Jaroszewski, Jerzy W; Olafsdottir, Elin Soffia.

In: Phytochemistry, Vol. 71, No. 2-3, 2010, p. 149-157.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Halldórsdóttir, ES, Jaroszewski, JW & Olafsdottir, ES 2010, 'Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre', Phytochemistry, vol. 71, no. 2-3, pp. 149-157. https://doi.org/10.1016/j.phytochem.2009.10.018

APA

Halldórsdóttir, E. S., Jaroszewski, J. W., & Olafsdottir, E. S. (2010). Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre. Phytochemistry, 71(2-3), 149-157. https://doi.org/10.1016/j.phytochem.2009.10.018

Vancouver

Halldórsdóttir ES, Jaroszewski JW, Olafsdottir ES. Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre. Phytochemistry. 2010;71(2-3):149-157. https://doi.org/10.1016/j.phytochem.2009.10.018

Author

Halldórsdóttir, Elsa Steinunn ; Jaroszewski, Jerzy W ; Olafsdottir, Elin Soffia. / Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre. In: Phytochemistry. 2010 ; Vol. 71, No. 2-3. pp. 149-157.

Bibtex

@article{dd9e7b20042b11df825d000ea68e967b,
title = "Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre",
abstract = "The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M, anhydrolycodoline, gnidioidine, lycofoline, lannotinidine D, and acrifoline, as well as a previously unknown N-oxide of annotine. (1)H and (13)C NMR data of several of the alkaloids were provided for the first time. Solvent-dependent equilibrium constants between ketone and hemiketal form of acrifoline were determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the active site gorge of the enzyme but the position of their functional groups is not compatible with establishing strong hydrogen bonding interactions with the amino acid residues that line the binding site. The docking studies indicate possibilities of additional functionalization of the lycopodane skeleton to render potentially more active analogues.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Halld{\'o}rsd{\'o}ttir, {Elsa Steinunn} and Jaroszewski, {Jerzy W} and Olafsdottir, {Elin Soffia}",
note = "Keywords: Lycopodium annotinum; Lycopodiacea; Alkaloids; NMR spectroscopy; Acetylcholinesterase; Butyrylcholinesterase; Ligand docking",
year = "2010",
doi = "10.1016/j.phytochem.2009.10.018",
language = "English",
volume = "71",
pages = "149--157",
journal = "Phytochemistry",
issn = "0031-9422",
publisher = "Pergamon Press",
number = "2-3",

}

RIS

TY - JOUR

T1 - Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre

AU - Halldórsdóttir, Elsa Steinunn

AU - Jaroszewski, Jerzy W

AU - Olafsdottir, Elin Soffia

N1 - Keywords: Lycopodium annotinum; Lycopodiacea; Alkaloids; NMR spectroscopy; Acetylcholinesterase; Butyrylcholinesterase; Ligand docking

PY - 2010

Y1 - 2010

N2 - The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M, anhydrolycodoline, gnidioidine, lycofoline, lannotinidine D, and acrifoline, as well as a previously unknown N-oxide of annotine. (1)H and (13)C NMR data of several of the alkaloids were provided for the first time. Solvent-dependent equilibrium constants between ketone and hemiketal form of acrifoline were determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the active site gorge of the enzyme but the position of their functional groups is not compatible with establishing strong hydrogen bonding interactions with the amino acid residues that line the binding site. The docking studies indicate possibilities of additional functionalization of the lycopodane skeleton to render potentially more active analogues.

AB - The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M, anhydrolycodoline, gnidioidine, lycofoline, lannotinidine D, and acrifoline, as well as a previously unknown N-oxide of annotine. (1)H and (13)C NMR data of several of the alkaloids were provided for the first time. Solvent-dependent equilibrium constants between ketone and hemiketal form of acrifoline were determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the active site gorge of the enzyme but the position of their functional groups is not compatible with establishing strong hydrogen bonding interactions with the amino acid residues that line the binding site. The docking studies indicate possibilities of additional functionalization of the lycopodane skeleton to render potentially more active analogues.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.phytochem.2009.10.018

DO - 10.1016/j.phytochem.2009.10.018

M3 - Journal article

C2 - 19939421

VL - 71

SP - 149

EP - 157

JO - Phytochemistry

JF - Phytochemistry

SN - 0031-9422

IS - 2-3

ER -

ID: 17078652