Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor

The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of...

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Main Authors:	Chean, Hui Ng, Rullah, Kamal, Mohd Aluwi, Mohd Fadhlizil Fasihi, Abas, Faridah, Kok, Wai Lam, Ismail, Intan Safinar, Narayanaswamy, Radhakrishnan, Jamaludin, Fadzureena, Shaari, Khozirah
Format:	Article
Language:	English
Published:	MDPI 2014
Subjects:	RS403 Materia Medica-Pharmaceutical Chemistry
Online Access:	http://irep.iium.edu.my/73318/ http://irep.iium.edu.my/73318/ http://irep.iium.edu.my/73318/1/Kamal%20Rullah%203.pdf

id	iium-73318
recordtype	eprints
spelling	iium-733182019-07-25T07:35:08Z http://irep.iium.edu.my/73318/ Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor Chean, Hui Ng Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Abas, Faridah Kok, Wai Lam Ismail, Intan Safinar Narayanaswamy, Radhakrishnan Jamaludin, Fadzureena Shaari, Khozirah RS403 Materia Medica-Pharmaceutical Chemistry The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Herein, we report the synthesis of tHGA analogs using simple Friedel-Craft acylation and alkylation reactions with the aim of obtaining a better insight into the structure-activity relationships of the compounds. All the synthesized analogs showed potent soybean 15-LOX inhibitory activity in a dose-dependent manner (IC50 = 10.31–27.61 μM) where compound 3e was two-fold more active than tHGA. Molecular docking was then applied to reveal the important binding interactions of compound 3e in soybean 15-LOX binding site. The findings suggest that the presence of longer acyl bearing aliphatic chain (5Cs) and aromatic groups could significantly affect the enzymatic activity MDPI 2014-08-05 Article PeerReviewed application/pdf en http://irep.iium.edu.my/73318/1/Kamal%20Rullah%203.pdf Chean, Hui Ng and Rullah, Kamal and Mohd Aluwi, Mohd Fadhlizil Fasihi and Abas, Faridah and Kok, Wai Lam and Ismail, Intan Safinar and Narayanaswamy, Radhakrishnan and Jamaludin, Fadzureena and Shaari, Khozirah (2014) Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor. Molecules, 19 (8). pp. 11645-11659. ISSN 1420-3049 https://www.mdpi.com/1420-3049/19/8/11645
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RS403 Materia Medica-Pharmaceutical Chemistry
spellingShingle	RS403 Materia Medica-Pharmaceutical Chemistry Chean, Hui Ng Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Abas, Faridah Kok, Wai Lam Ismail, Intan Safinar Narayanaswamy, Radhakrishnan Jamaludin, Fadzureena Shaari, Khozirah Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
description	The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Herein, we report the synthesis of tHGA analogs using simple Friedel-Craft acylation and alkylation reactions with the aim of obtaining a better insight into the structure-activity relationships of the compounds. All the synthesized analogs showed potent soybean 15-LOX inhibitory activity in a dose-dependent manner (IC50 = 10.31–27.61 μM) where compound 3e was two-fold more active than tHGA. Molecular docking was then applied to reveal the important binding interactions of compound 3e in soybean 15-LOX binding site. The findings suggest that the presence of longer acyl bearing aliphatic chain (5Cs) and aromatic groups could significantly affect the enzymatic activity
format	Article
author	Chean, Hui Ng Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Abas, Faridah Kok, Wai Lam Ismail, Intan Safinar Narayanaswamy, Radhakrishnan Jamaludin, Fadzureena Shaari, Khozirah
author_facet	Chean, Hui Ng Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Abas, Faridah Kok, Wai Lam Ismail, Intan Safinar Narayanaswamy, Radhakrishnan Jamaludin, Fadzureena Shaari, Khozirah
author_sort	Chean, Hui Ng
title	Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
title_short	Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
title_full	Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
title_fullStr	Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
title_full_unstemmed	Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
title_sort	synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor
publisher	MDPI
publishDate	2014
url	http://irep.iium.edu.my/73318/ http://irep.iium.edu.my/73318/ http://irep.iium.edu.my/73318/1/Kamal%20Rullah%203.pdf
first_indexed	2023-09-18T21:43:56Z
last_indexed	2023-09-18T21:43:56Z
_version_	1777413324147785728

Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor

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