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

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

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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

Item Type: Article (Journal)
Additional Information: 9020/73318
Uncontrolled Keywords: lipoxygenase; analogs; Friedel-Craft acylation; Friedel-Craft alkylation; molecular docking
Subjects: R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy
Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Dr Kamal Rullah
Date Deposited: 25 Jul 2019 15:35
Last Modified: 25 Jul 2019 15:35
URI: http://irep.iium.edu.my/id/eprint/73318

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