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Design of xanthorrhizol derivatives using in silico fragment-based drug design (FBDD) approach as lipoxygenase inhibitors

Tengku Nazmi, Tengku Kamilah and Aminudin, Nurul Iman and Hamzah, Nurasyikin (2023) Design of xanthorrhizol derivatives using in silico fragment-based drug design (FBDD) approach as lipoxygenase inhibitors. In: Postgraduate Colloquium 2023, 9 Oct 2023, Kuantan, Malaysia. (Unpublished)

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PURPOSE: Xanthorrhizol (XNT), a natural product isolated from Curcuma xanthorrhiza is known for its anti-inflammatory properties, through inhibition of pro-inflammatory enzymes, such as cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS). Due to its small molecular weight (MW=281.33 g/mol) and biological activity, XNT is a suitable candidate to be further optimized as a more potent anti-inflammatory agent. Preliminary in vitro inhibitory studies showed that XNT exhibited mild activity (50.01% inhibition at concentration 100 µg/mL) against lipoxygenase (sLOX), an enzyme responsible for the eicosanoids biosynthesis pathway to form leukotrienes, that can induce inflammatory response towards human body. Hence, we aimed to improve the activity of XNT towards sLOX by modifying its hydroxyl functionality using combination of in silico methods, which are molecular docking and fragment-based drug design (FBDD) approach. In this study, a total of 1887 new XNT derivatives were generated as sLOX inhibitors by using LigBuilder software. Then, only the top 50 derivatives which exhibit binding energies, ranging from -8.4 to -9.0 kcal/mol were screened to remove duplicates. The number of derivates were further narrowed based on its ADME and druglikeness properties. Five promising XNT derivatives were chosen, consisting of different long alkyl chain with different heteroatoms, as potential Hyal inhibitors to be synthesized in the future. This work provided a more efficient approach for drug modification to produce more potent novel compounds using computational methods.

Item Type: Proceeding Paper (Poster)
Additional Information: 8125/107409
Uncontrolled Keywords: Xanthorrhizol, lipoxygenase, in silico FBDD, molecular docking, ADME profile
Subjects: Q Science > QD Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Science
Kulliyyah of Science > Department of Chemistry
Depositing User: Dr Nurul Iman Aminudin
Date Deposited: 10 Nov 2023 16:56
Last Modified: 16 Nov 2023 14:29
URI: http://irep.iium.edu.my/id/eprint/107409

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