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. 2023 Nov 1;13(11):2152.
doi: 10.3390/life13112152.

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

Sibhghatulla Shaikh  1   2 , Shahid Ali  1   2 , Jeong Ho Lim  1   2 , Khurshid Ahmad  1   2 , Ki Soo Han  3 , Eun Ju Lee  1   2 , Inho Choi  1   2
Affiliations

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

Sibhghatulla Shaikh et al. Life (Basel). .

Abstract

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 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 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 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, 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 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA.

Keywords: 5α-reductase type II; androgen; androgenic alopecia; dihydrotestosterone; natural compounds.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Visualization of finasteride (black), eriocitrin (red), and silymarin (cyan) in the 5αR2 binding pocket (A). 2D views of 5αR2 residues interacting with eriocitrin (B), silymarin (C), and finasteride (D).
Figure 2
Figure 2
MD simulation studies of docked complexes. RMSD plot (A), average RMSD plot (B), RMSD plots of ligands in the 5αR2 catalytic pocket (C), and corresponding RMSF plots (D). Black, red, and cyan indicate finasteride, eriocitrin, and silymarin, respectively.
Figure 3
Figure 3
Rg plot of complexes (A), SASA plot (B), number of H-bonds formed with ligands (C), and MSD plot (D). Black, red, and cyan indicate finasteride, eriocitrin, and silymarin, respectively.
Figure 4
Figure 4
2D projections of complexes (A) and Gibbs energy landscape plots (B–D).
See this image and copyright information in PMC

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