Several studies have reported that certain cannabinoid derivatives may affect prostate cancer progression. However, their specific actions on the androgen receptor and the 5α-reductase enzyme remain ambiguous, likely due to the structural variability among cannabinoid compounds. This computational investigation aimed to explore the theoretical interactions of 20 distinct cannabinoid derivatives (identified as compounds 1 through 20) with the androgen receptor and the 5α-reductase enzyme, using the protein models 3L3X and 7BW1, respectively. In addition, reference ligands such as testosterone, dihydrotestosterone, flutamide, finasteride, and dutasteride were incorporated as standard molecular tools in the analysis. The findings showed that derivatives 6, 13, 16, and 20 demonstrated superior binding affinity to the androgen receptor in comparison to testosterone, dihydrotestosterone, and flutamide. In addition, the data also indicated that compounds 1, 3, 14, and 18 showed a stronger theoretical interaction with 5α-reductase than dutasteride and finasteride. These results suggest that compounds 6, 13, 16, and 20 may act as potential androgen receptor inhibitors, while derivatives 1, 3, 14, and 18 may act as inhibitors of the 5α-reductase enzyme. These interactions highlight the therapeutic promise of these cannabinoid analogs in the context of prostate cancer management.
