A Comprehensive In Silico Exploration of Pharmacological Properties, Bioactivities, Molecular Docking, and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase.

Syed Shams Ul Hassan,Simona G Bungau,Muhammad Ishaq,Hui-Zi Jin,Iqra Bano,Syed Qamar Abbas,Fawad Ali,Mubashir Hassan

doi:10.3390/molecules27030917

Abstract

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with −11.8 kcal/mol energy than control vemurafenib −10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme’s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.

Highlights

Melanoma is the most aggressive and deadly form of skin cancer [1,2,3,4]
The chemical structure of a guaiane dimer vieloplain F was drawn on ChemBioDraw (v13.0) and the control drug vemurafenib was downloaded from PubChem and was redrawn on ChemBioDraw (Figure 1)
The probable activity (Pa) values were higher than Pa > 0.5, and the probable inactivity (Pi) scores were extremely near to 0, demonstrating that the compound is highly expected to demonstrate these activities

Summary

Introduction

Melanoma is the most aggressive and deadly form of skin cancer [1,2,3,4]. It is the seventh leading cancer in women and fifth in men in the USA [5,6]. BRAF inhibitors, such as vemurafenib, are the most effective FDA-approved treatments for BRAF positive melanoma. The negative side of the drug vemurafenib is that patients started getting resistance after six months of therapy, making therapy no longer effective [8]. More effective treatments are urgently needed as the prevalence of melanoma rises in the United States and other developed nations

Results

Discussion

Conclusion