Computational discovery of resiniferatoxin and euphol as potential androgen receptor inhibitors for prostate cancer therapy.

Prostate cancer is one of the most common malignancies in men worldwide and is driven in large part by aberrant androgen receptor (AR) signaling. Upon sufficient androgenic concentration, the AR undergoes conformational changes and translocates to the nucleus, where it promotes the transcription of genes essential for tumor growth and progression. In this study, we performed a structure-based virtual screening of 34 phytochemicals from Euphorbia resinifera against the crystal structure of the AR ligand-binding domain (PDB ID: 1E3G). This screening identified two leading compounds, Resiniferatoxin and Euphol, both demonstrated favorable binding poses and docking scores of -10 kcal/mol and -8.6 kcal/mol, respectively, surpassing Flutamide, the standard antiandrogen (-7.7 kcal/mol). Furthermore, a 100 ns molecular dynamics simulation showed that these two molecules formed stable complexes with AR, suggesting their potential utility as natural AR inhibitors in prostate cancer therapy. However, additional experimental studies are essential to validate their efficacy, elucidate their mechanisms of action, and assess their safety profiles, potentially paving the way for innovative plant-based treatments targeting AR-driven prostate cancer.