Computational Exploration of Anti-Cancer Potential of GUAIANE Dimers from <i>Xylopia vielana</i> 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*   Pages 731 - 746 ( 16 )

Abstract:

Background: Natural products from herbs are abundant and display powerful anti-cancer activities. <P> 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 <i>Xylopia vielana</i>. <P> Methods: In this work, a systematic <i>in silico</i> study using ADMET analysis, bioactivity score forecasts, and molecular docking along with its simulations was conducted to understand compounds’ pharmacological properties. <P> 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. <P> 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 <i>in silico</i> approach for creating an anti-cancer pathway for guaiane dimers against the backdrop of its potential for future drug development.

Keywords:

<i>Xylopia vielana</i>, B-Raf kinase, melanoma, molecular docking, ADMET, MD simulations.

Affiliation:

Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, Institute of Molecular Biology and Biotechnology, The University of Lahore, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240

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