Rotenoids from the Roots of <i>Vicia faba</i> L. (Fabaceae): Structural Characterization, Cytotoxic Effects, and Molecular Docking

The chemical study of the ethanolic extract from the roots of Vicia faba led to the isolation of two isoflavonoids, alfalone and 8-O-methylretusine, as well as a mixture of rotenoids, including clitoriacetal and clitoriacetal B, the latter of which is reported for the first time. These compounds were characterized through nuclear magnetic resonance and vibrational circular dichroism spectroscopies, and density functional theory calculations. The rotenoid mixture exhibited cytotoxic activity against HCT-116, MCF-7, and 501Mel cell lines, while showing no significant toxicity to NIH/3T3 cells. The predictive analysis identified several shared therapeutic targets across colorectal cancer, breast cancer, and melanoma. Key sites, including hypoxia-inducible factor 1-alpha (HIF1A), estrogen receptor, heat shock protein HSP 90-beta, and heat shock protein HSP 90-alpha, were highlighted for their critical roles in tumor progression and therapeutic resistance. Notably, clitoriacetal demonstrated an affinity for HIF1A, suggesting its involvement in the observed antitumor effects, likely through modulation of the HIF1A pathway. These findings underscore the potential of V. faba root-derived compounds as promising candidates for targeted cancer therapies.