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 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.