Bryophyllin C and Its Therapeutic Role in Breast Cancer: Insights from Density Functional Theory to Molecular Dynamics

Bryophillin C (BRYOC), a bufadienolide present in plants of the Kalanchoe genus, has been scarcely explored in scientific literature, and its interaction with proteins involved in breast cancer (BCa) pathophysiology is yet to be understood. This study aimed to explore BRYOC’s anticancer potential in BCa using computational methods. Density functional theory (DFT) analysis revealed a HOMO–LUMO gap of 4.59 eV, suggesting moderate chemical reactivity and polarizability. The predicted ADMET profile suggested good oral bioavailability and limited distribution potential in the body. Databases helped identify BRYOC targets and genes linked to BCa, which are mainly involved in protein autophosphorylation and transmembrane receptor protein tyrosine kinase activity. A protein–protein interaction network was constructed to identify the main targets connecting BRYOC and BCa. Molecular docking studies indicated that SRC, PIK3CA, and ESR1 exhibited the most favorable binding affinities. To assess complex stability, a 100 ns molecular dynamics simulation was conducted, followed by a detailed examination of key structural parameters, such as the root-mean-square deviation and radius of gyration. MM/GBSA calculations predicted favorable binding free energies for SRC and ESR1 ligands. These results emphasize the importance of these proteins as therapeutic targets in the pathophysiology of BCa and serve as a precedent for future studies focused on BRYOC and its possible anticancer effects.