Comparative Molecular Docking Analysis, of Natural and Synthetic Ligands, Targeting BRCA1, BRCA2, ER, and PR in Breast Cancer Treatment

Abstract

Objective: Breast cancer remains a leading cause of cancer-related mortality in women, necessitating the development of innovative therapeutic strategies. This study employs comparative molecular docking to evaluate the binding affinities of natural compounds, derived from a specifically formulated oil mixture, against key molecular targets in breast cancer BRCA1, BRCA2, estrogen receptor (ER), and progesterone receptor (PR). Methods: Synthetic ligands commonly used in breast cancer therapy were included as reference compounds. Molecular docking was performed using 1-Click Docking software to determine binding energy values, expressed in kcal/mol, with more negative ΔG values indicating stronger and more spontaneous ligand-receptor interactions. Results: Among the synthetic ligands, Epirubicin exhibited the highest binding affinity to BRCA2 (-9.0 kcal/mol), while Capecitabine demonstrated the strongest interaction with PR (-8.1 kcal/mol). Notably, the natural compound Narirutin outperformed these drugs, showing a superior binding affinity to BRCA2 (-9.2 kcal/mol) and PR (-8.9 kcal/mol). Additionally, Geraniol and Citronellol exhibited competitive binding affinities to ER and PR, respectively, underscoring their potential therapeutic relevance. These findings highlight the capability of natural compounds to act as effective inhibitors of critical breast cancer molecular targets. Narirutin, in particular, stands out as a promising candidate for further exploration in integrative cancer therapies. Conclusion: This study demonstrates the utility of bioinformatics approaches, specifically molecular docking, in identifying natural compounds with high therapeutic potential and provides a computational framework for future experimental validation and drug development.