Theoretical Evaluation of Twenty-Cannabinoid Derivatives on Either Androgen Receptor or 5α-Reductase Enzyme

There are studies which suggest that some cannabinoids derivatives can produce effects on prostate cancer; however, the effect exerted on androgen receptor and 5a-reductase is very confusing; perhaps, this phenomenon is due to differences in the chemical structure of cannabinoids. The aim of this theoretical research was to evaluate the possible interaction of twenty-cannabinoids derivatives (compounds 1 to 20) with either androgen receptor or 5a-reductase enzyme using either 3L3X or 7BW1 proteins as the theoretical models. Besides, testosterone, dihydrotestosterone, dutasteride, finasteride and flutamide drugs were used as theoretical tools. The results showed higher affinity of cannabinoid derivatives 6, 13, 16 and 20 for the androgen receptor surface compared to testosterone, dihydrotestosterone and flutamide. In addition, other data indicate that cannabinoid derivatives 1, 3, 14 and 18 could have higher affinity by 5a-reductase enzyme compared with dutasteride and finasteride. All these data suggest that cannabinoid derivatives 6, 13, 16 and 20 could act as androgen receptor inhibitors. In addition, the cannabinoid analogs 1, 3, 14 and 18 could exert their biological activity as 5a-reductase enzyme inhibitors. This phenomenon could be translated as good candidates for the treatment of prostate cancer.