New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights

Muhammad Nadeem Akhtar, Kok Wai Lam, Faridah Abas, Maulidiani, Syahida Ahmad, Syed Adnan Ali Shah, Atta-Ur-Rahman, M. Iqbal Choudhary, Nordin Hj Lajis

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Bioassay-guided extraction of the stem bark of Knema laurina showed the acetylcholinesterase (AChE) inhibitory activity of DCM and hexane fractions. Further repeated column chromatography of hexane and DCM fractions resulted in the isolation and purification of five alkenyl phenol and salicylic acid derivatives. New compounds, (+)-2-hydroxy-6-(10′-hydroxypentadec- 8′(E)-enyl)benzoic acid (1) and 3-pentadec-10′(Z)-enylphenol (2), along with known 3-heptadec-10′(Z)-enylphenol (3), 2-hydroxy-6-(pentadec- 10′(Z)-enyl)benzoic acid (4), and 2-hydroxy-6-(10′(Z)-heptadecenyl) benzoic acid (5) were isolated from the stem bark of this plant. Compounds (1-5) were tested for their acetylcholinesterase inhibitory activity. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and chemical derivatizations. Compound 5 showed strong acetylcholinesterase inhibitory activity with IC 50 of 0.573 ± 0.0260 μM. Docking studies of compound 5 indicated that the phenolic compound with an elongated side chain could possibly penetrate deep into the active site of the enzyme and arrange itself through π-π interaction, H-bonding, and hydrophobic contacts with some critical residues along the complex geometry of the active gorge.

Original languageEnglish
Pages (from-to)4097-4103
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number13
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

Fingerprint

Benzoic Acid
Cholinesterase Inhibitors
Acetylcholinesterase
Hexanes
Plant Bark
Plant Stems
Column chromatography
Salicylic Acid
Bioassay
Phenol
Biological Assay
Nuclear magnetic resonance spectroscopy
Purification
Mass spectrometry
Chromatography
Mass Spectrometry
Catalytic Domain
Magnetic Resonance Spectroscopy
Derivatives
Geometry

Keywords

  • Acetylcholinesterase inhibition
  • Alkyl resorcinol
  • Knema laurina
  • Molecular docking
  • Myristicaceae

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights. / Akhtar, Muhammad Nadeem; Lam, Kok Wai; Abas, Faridah; Maulidiani; Ahmad, Syahida; Shah, Syed Adnan Ali; Atta-Ur-Rahman; Choudhary, M. Iqbal; Lajis, Nordin Hj.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 13, 01.07.2011, p. 4097-4103.

Research output: Contribution to journalArticle

Akhtar, MN, Lam, KW, Abas, F, Maulidiani, Ahmad, S, Shah, SAA, Atta-Ur-Rahman, Choudhary, MI & Lajis, NH 2011, 'New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 13, pp. 4097-4103. https://doi.org/10.1016/j.bmcl.2011.04.065
Akhtar, Muhammad Nadeem ; Lam, Kok Wai ; Abas, Faridah ; Maulidiani ; Ahmad, Syahida ; Shah, Syed Adnan Ali ; Atta-Ur-Rahman ; Choudhary, M. Iqbal ; Lajis, Nordin Hj. / New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 13. pp. 4097-4103.
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