Virtual Insights into Natural Compounds as Potential 5-Reductase Type II Inhibitors: A Structure-Based Screening and Molecular Dynamics Simulation Study

Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5 alpha-reductase type II (5 alpha R2), which is expressed in scalp hair follicles; 5 alpha R2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5 alpha R2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5 alpha R2, with binding energies of -12.1 and -11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (-11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5 alpha R2 and revealed that the interaction of eriocitrin and silymarin with 5 alpha R2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5 alpha R2 inhibitors for the management of AGA.