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. 2022 Jan 28;27(3):917.
doi: 10.3390/molecules27030917.

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  1   2 , Syed Qamar Abbas  3 , Fawad Ali  4 , Muhammad Ishaq  1   2 , Iqra Bano  5 , Mubashir Hassan  6   7 , Hui-Zi Jin  1   2 , Simona G Bungau  8
Affiliations

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 et al. Molecules. .

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.

Keywords: ADMET; MM-GBSA; guaiane dimer; melanoma; molecular docking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of (a) vieloplain F; (b) vemurafenib.
Figure 2
Figure 2
(a) Bioavailability radar chart for vieloplain F. The pink zone represents the physicochemical space for oral bioavailability, and the red line represents the oral bioavailability properties. (b) Predicted BOILED-Egg plot from swiss ADME online web tool for all the compounds.
Figure 3
Figure 3
Cardiac toxicity of drugs derived from pred-hERG in a map format: (a) vieloplain F; (b) vemurafenib.
Figure 4
Figure 4
Prediction of epoxidation and reactivity to biological macromolecules by XenoSite. (a) The input structure of vieloplain F; (b) prediction of epoxidation; prediction of reactivity to: (c) cyanide; (d) DNA; (e) glutathione (GSH); (f) protein; (g) the input structure of vemurafenib; (h) prediction of epoxidation; prediction of reactivity to: (i) cyanide; (j) DNA; (k) glutathione (GSH); (l) protein.
Figure 5
Figure 5
Endocrine disruption potential of compounds as obtained from Endocrine Disruptome. (a) Vieloplain F, (b) vemurafenib. Red color describes the high probability of binding, Orange and Yellow describes the medium probability of binding while the Green color describes the low probability binding.
Figure 6
Figure 6
(a) 2D interactions of the compound vieloplain F with B-Raf (PDB: 3OG7); (b) 2D interactions of the control vemurafenib with B-Raf (PDB: 3OG7).
Figure 7
Figure 7
Root mean square deviation (RMSD) of the (a) vemurafenib–B-Raf kinase; (b) vieloplain-F–B-Raf kinase.
Figure 8
Figure 8
Root mean square fluctuation (RMSF) of protein complexes (a) vemurafenib–B-Raf kinase, (b) vieloplain-F–B-Raf kinase.
Figure 9
Figure 9
Protein secondary structure element distribution by residue index throughout the protein structures complexed with ligand (a) vemurafenib–B-Raf kinase, (b) vieloplain-F–B-Raf kinase. The red color represents α-helices, and the blue represents β-strands.
Figure 10
Figure 10
Protein–ligand contact histogram: (a) vemurafenib–B-Raf kinase, (b) vieloplain-F–B-Raf kinase.
Figure 11
Figure 11
The radius of gyration was calculated for (a) vemurafenib–B-Raf kinase, (b) vieloplain-F–B-Raf kinase.
Figure 12
Figure 12
MM-GBSA calculated before and after the simulation.
See this image and copyright information in PMC

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