Phytochemical baicalin potentially inhibits Bcl-2 and VEGF: an in silico approach.

Abstract

Background: The rising prevalence of cancer cells exhibits uncontrolled growth and invasive and aggressive properties, leading to metastasis, which poses a significant challenge for global health. Central to cancer development are proteins such as NF-kB, p53, VEGF, and BAX/Bcl-2, which play important roles in angiogenesis, cell apoptosis regulation, and tumor growth.

Methodology: This in silico study evaluates the activity of six different natural as well as novel therapeutic strategies against cancer. Using a computational approach, i.e., virtual screening, molecular docking, and molecular dynamics (MD) simulations, the binding affinities and interactions of selected phytochemicals with cancer-specific proteins were analyzed. Key criteria for selection included binding affinity, molecular stability, and pharmacokinetic and toxicological properties. Post-selection, dynamics of ligand-protein interactions were further examined through MD simulations conducted using Desmond-Maestro 2020-4 on a Linux-based HP Z2 workstation, providing an insight into the conformational changes in the stability of the inhibitor-protein complexes. This was complemented by ADMET predictions to assess pharmacokinetics and toxicological profiles.

Results: Our findings reveal that out of six phytochemicals, baicalin exhibited the most promising results, with docking scores of -9.2 kcal/mol and -9.0 kcal/mol against Bcl-2 and VEGF receptors, respectively. The MD simulation (100 ns) confirmed the stability of baicalin-protein interactions, supported by hydrophobic interactions and intermolecular hydrogen bonds. The RMSD and RMSF values of baicalin exhibit an acceptable global minimum (3.5-6 Å) for p53, VEGF, and BAX/Bcl-2.

Conclusion: This study highlights the potential of baicalin, a phytochemical known for anti-cancerous, anti-apoptotic, and anti-proliferative properties, as a promising candidate for cancer treatment. Further exploration and validation of its inhibitory mechanisms could open a promising avenue for therapeutic approaches in oncology.