Comprehensive pharmacokinetic profiling and molecular docking analysis of natural bioactive compounds targeting oncogenic biomarkers in breast cancer

Breast cancer is one of the leading causes of death in women worldwide, highlighting the crucial need for novel and effective treatments. In this study, we look at the ability of four natural compounds i.e. Berberine, Curcumin, Withaferin A, and Ellagic Acid to target important breast cancer biomarkers such as B-cell lymphoma 2 (BCL-2), programmed death-ligand 1 (PDL-1), cyclin-dependent kinase 4/6 (CDK4/6) and fibroblast growth factor receptor (FGFR). These indicators have important roles in tumor development, survival, immune response, and cell cycle control, making them potential targets for future cancer treatments. Our study employs a variety of techniques, including pharmacokinetic profiling (ADME), molecular docking, and molecular dynamics simulations, to determine how successful these drugs could be in therapy. The pharmacokinetic investigation found that Berberine and Ellagic Acid stand out due to their high absorption and solubility, implying that they could be suitable for clinical application. When we ran docking simulations, we discovered substantial connections between these chemicals and the target proteins. Additionally, Berberine has a binding affinity of - 9.3 kcal/mol for BCL-2, indicating that it can impair the protein's cancer cell-protective activities. Ellagic Acid, on the other hand, has an even higher binding affinity for PDL-1 of - 9.8 kcal/mol, showing that it may be able to increase immune responses against tumors. Molecular dynamics simulations over 100 ns demonstrated the stability of these protein-ligand complexes. Interestingly, Ellagic Acid was found to be more structurally stable than Berberine throughout these simulations. We found consistent interactions between the chemicals and key residues in the target proteins. For example, Ellagic Acid (CID: 5281855) established persistent linkages with LYS43, ASP163, and VAL27, whereas Berberine (CID: 2353) interacted with VAL27, ALA41, and LEU152 throughout the simulation. In conclusion, the combination of good pharmacokinetics, robust interactions with cancer biomarkers, and stable complexes makes Berberine and Ellagic Acid interesting candidates for further investigation as natural inhibitors in breast cancer treatment. These findings establish the framework for future research into novel and inventive techniques to effectively combating breast cancer.