VIKAS SHARMA ¹ Arti Gupta ² Mohini Singh ¹ Anshul Singh ¹ Anis Ahmad Chaudhary ³ Ashraf Ahmad Qurtam ³ Salah-Ud-Din Khan ⁴ Sarvesh Rustagi ^5,6 Sanjay Kumar ^1* Sandeep Kumar Shukla ^1*

• ¹ Sharda University, Greater Noida, India
• ² Llyod School of Pharmacy,, Greater Noida, India
• ³ Department of Biology, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
• ⁴ Imam Muhammad ibn Saud Islamic University, Riyadh, Saudi Arabia
• ⁵ Department of Food Technology, College of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
• ⁶ Department of Homoeopathy, Government of Uttar Pradesh, Lucknow, Uttar Pradesh, India

The rising prevalence of cancer cells exhibit uncontrolled growth, invasive and aggressive properties leading to metastasis, which poses a significant challenge for global health. Central to the cancer development are proteins such as NF-kB, p53, VEGF, BAX/Bcl-2 which play important roles in angiogenesis, cell apoptosis regulation and tumor growth.This in-silico study evaluates the activity of six different natural as novel therapeutic strategies against cancer. Using a computational approach, i.e. virtual screening, molecular docking, molecular dynamics (MD) simulations to analyse the binding affinities and interactions of selected phytochemicals with cancer-specific proteins was conducted. Key criteria for selection included binding affinity, molecular stability, 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 insight into the conformational changes in stability of the inhibitor-protein complexes. This was complemented by ADMET predictions to assess pharmacokinetics and toxicological profiles.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 receptor, 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, BAX/Bcl-2.This study highlights the potential of baicalin, a phytochemical known for anti-cancerous, antiapoptotic, and antiproliferative 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.