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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Computational Exploration of Anti-Cancer Potential of GUAIANE Dimers from Xylopia vielana by Targeting B-Raf Kinase Using Chemo-Informatics, Molecular Docking, and MD Simulation Studies

Author(s): Syed Shams ul Hassan, Syed Qamar Abbas, Mubashir Hassan and Hui-Zi Jin*

Volume 22, Issue 4, 2022

Page: [731 - 746] Pages: 16

DOI: 10.2174/1871520621666211013115500

Abstract

Background: Natural products from herbs are abundant and display powerful anti-cancer activities.

Objectives: In the current study, B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma, was tested against two guaiane-type sesquiterpene dimers, xylopin E-F, obtained from Xylopia vielana.

Methods: In this work, a systematic in silico study using ADMET analysis, bioactivity score forecasts, and molecular docking along with its simulations was conducted to understand compounds’ pharmacological properties.

Results: During ADMET predictions of both the compounds, xylopin E-F displayed a safer profile in hepatotoxicity and cytochrome inhibition, and only xylopin F was shown to be non-cardiotoxic compared to the FDA-approved drug vemurafenib. Both the compounds were proceeded to molecular docking experiments using Autodock docking software, and both the compounds, xylopin E-F, displayed higher binding potential with -11.5Kcal/mol energy compared to control vemurafenib (-10.2 Kcal/mol). All the compounds were further evaluated for their MD simulations, and their molecular interactions with the B-Raf kinase complex displayed precise interactions with the active gorge of the enzyme by hydrogen bonding.

Conclusion: Overall, xylopin F had a better profile relative to xylopin E and vemurafenib, and these findings indicated that this bio-molecule could be used as an anti-melanoma agent and as a possible anti-cancer drug in the future. Therefore, this is a systematically optimized in silico approach for creating an anti-cancer pathway for guaiane dimers against the backdrop of its potential for future drug development.

Keywords: Xylopia vielana, B-Raf kinase, melanoma, molecular docking, ADMET, MD simulations.

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