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

Abstract

Background: Natural products from herbs are prolific to display robust anticancer 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, molecular docking, and its simulations were conducted to understand compounds' pharmacological properties. Results: During ADMET predictions of both the compounds, Xylopin E-F has displayed a safer profile in hepatotoxicity, cytochrome inhibition, and only xylopin F displayed as non-cardiotoxic compared to FDA approved drug vemurafenib. Both the compounds were proceeded to molecular docking experiments using Autodock docking software and both the compounds Xylopin E-F have 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. Conclusions: 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 anticancer drug in the future. Therefore, this is a systematic optimized in silico approach to creating an anticancer pathway for guaiane dimers against the backdrop of its potential for future drug development.