Exploring Promising Therapeutics of Flavonoids From Psoralea corylifolia Against Breast Cancer through Computational Approaches

Breast carcinoma stands as the most prevalent malignancy and a leading cause of oncological mortality in females globally. Plant-derived agents, particularly flavonoids, show considerable promise by inducing programmed cell death in neoplastic cells through multiple signaling pathways and by overcoming apoptosis resistance. The current examination assessed the anti-breast carcinoma potential of flavonoids extracted from Psoralea corylifolia L., emphasizing their affinity to Bcl-2 (PDB: 6QGG) using an exclusively in silico approach. The results indicate that psocorylin R (CPD1) may promote apoptosis via predicted Bcl-2 inhibition, with a docking affinity of -8.56 kcal/mol, exceeding Tamoxifen (-6.76 kcal/mol). Across 100 ns dynamics simulations, the CPD1-6QGG assembly demonstrated durability (RMSD 0.15-0.25 nm; Rg 1.4-1.5 nm) with sustained hydrogen bonding (0-6; average 3) and SASA oscillations of 75-90 nm². MM/GBSA analyses yielded a binding strength of -25.4 ± 6.37 kcal/mol for CPD1 versus -20.04 ± 4.42 kcal/mol for Tamoxifen, and DFT descriptors (e.g., ΔE = 2.44 eV) supported CPD1 interaction potential. Nevertheless, conclusions are limited by the absence of experimental validation, no in vitro/in vivo efficacy or safety assays, and by not assessing off-target effects or unintended covalent reactivity, warranting systematic experimental confirmation.