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

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...

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Main Authors: Akhtar, Muhammad Nadim, Lam, Kok Wai, Abas, Faridah, Maulidiani, Ahmad, Syahida, Shah, Syed Adnan Ali, Atta-ur-Rahman, Choudhary, Muhammad Iqbal, Lajis, Md. Nordin
Format: Article
Language:English
Published: Elsevier 2011
Online Access:http://psasir.upm.edu.my/id/eprint/24120/
http://psasir.upm.edu.my/id/eprint/24120/1/24120.pdf
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author Akhtar, Muhammad Nadim
Lam, Kok Wai
Abas, Faridah
Maulidiani,
Ahmad, Syahida
Shah, Syed Adnan Ali
Atta-ur-Rahman,
Choudhary, Muhammad Iqbal
Lajis, Md. Nordin
author_facet Akhtar, Muhammad Nadim
Lam, Kok Wai
Abas, Faridah
Maulidiani,
Ahmad, Syahida
Shah, Syed Adnan Ali
Atta-ur-Rahman,
Choudhary, Muhammad Iqbal
Lajis, Md. Nordin
author_sort Akhtar, Muhammad Nadim
building UPM Institutional Repository
collection Online Access
description 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.
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spelling upm-241202016-04-28T05:25:03Z http://psasir.upm.edu.my/id/eprint/24120/ New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights Akhtar, Muhammad Nadim Lam, Kok Wai Abas, Faridah Maulidiani, Ahmad, Syahida Shah, Syed Adnan Ali Atta-ur-Rahman, Choudhary, Muhammad Iqbal Lajis, Md. Nordin 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. Elsevier 2011-07-01 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/24120/1/24120.pdf Akhtar, Muhammad Nadim and Lam, Kok Wai and Abas, Faridah and Maulidiani, and Ahmad, Syahida and Shah, Syed Adnan Ali and Atta-ur-Rahman, and Choudhary, Muhammad Iqbal and Lajis, Md. Nordin (2011) New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights. Bioorganic & Medicinal Chemistry Letters, 21 (13). pp. 4097-4103. ISSN 0960-894X; ESSN: 1464-3405 http://www.sciencedirect.com/science/article/pii/S0960894X11005245?np=y 10.1016/j.bmcl.2011.04.065
spellingShingle Akhtar, Muhammad Nadim
Lam, Kok Wai
Abas, Faridah
Maulidiani,
Ahmad, Syahida
Shah, Syed Adnan Ali
Atta-ur-Rahman,
Choudhary, Muhammad Iqbal
Lajis, Md. Nordin
New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title_full New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title_fullStr New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title_full_unstemmed New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title_short New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights
title_sort new class of acetylcholinesterase inhibitors from the stem bark of knema laurina and their structural insights
url http://psasir.upm.edu.my/id/eprint/24120/
http://psasir.upm.edu.my/id/eprint/24120/
http://psasir.upm.edu.my/id/eprint/24120/
http://psasir.upm.edu.my/id/eprint/24120/1/24120.pdf