Scientific African (Sep 2024)
Bioprospecting of potential inhibitors of 5alpha reductase 2 inhibitors from relevant ethno-pharmacological plants via in silico techniques
Abstract
Approximately 60 % of men globally over the age of 50 experience a diminished quality of life as a result of benign prostatic hyperplasia (BPH). Consequently, while the national direct cost for managing BPH is hovering around $4 billion in the USA, the individual direct cost for medications is estimated at $1536 and $425 annually for the USA and Ghana, respectively. Due to the chemotherapeutic drawbacks in BPH treatment, a concerted effort is urgently needed to find new chemotypes with novel mechanism of action to combat the disease. This research aims to employ computational techniques to identify new compounds from ethno-pharmacological plants from Ghana for treating BPH. Altogether, 250 natural products from Croton membranaceus, Heliotropium angiospermum, Annona muricata, Serenoa repens, Cissus quadrangularis, Tribulus terrestrials, Vernonia amagdalina and Momordica foetida from Ghanaian origin were virtually screened against 5alpha reductase 2 (5aR2), a primary drug target implicated in the parthenogenesis of BPH. Out of the 254 compounds docked, three compounds (A, B and C) showed a binding energy lower than testosterone (-10.4 kcal/mol), the main substrate of the target and comparative to finasteride (-11.7 kcal/mol), one of the drugs currently used for treating the disease. Molecular docking and dynamics simulations studies revealed Leu224 to be critical for ligand binding and complex stability. The pharmacological and physicochemical profiles show the compounds to possess good pharmacodynamics with negligible toxicities. While the compounds A, C, G, H, I and J were, respectively, predicted to treat prostate disorders with Pa (0.909, 0.221, 0.743, 0.729, 0.978, and 0.443) and Pi (0.003, 0.132, 0.005,0.005, 0.002, 0.016), that of A, B, D, G, H, I, and J were found to be associated with the inhibition of 5alpha reductase with Pa (0.840, 0.102, 0.097, 0.377, 0.123, 0.909, and 0.201) and Pi (0.001, 0.075, 0.089, 0.003, 0.036, 0.001, and 0.004), respectively. These lead-like compounds possessing plausible chemotherapeutic moieties with putative 5aR2 inhibitory potential need further experimental validation via in vitro studies.
