https://orcid.org/0000-0002-9740-3441
Abstract
Background: 5α-Reductase type II (5αR2) inhibition is a promising strategy for benign prostatic hyperplasia treatment. A computational approach including virtual screening, ligand-based 3D pharmacophore modeling, 2D quantitative structure–activity relationship and molecular docking simulations were adopted to develop novel inhibitors. Results: Hits were first filtered via the validated pharmacophore and 2D quantitative structure–activity relationship models. Docking on the recently determined cocrystallized structure of 5αR2 showed three promising hits. Visual inspection results were compared with finasteride ligand and dihydrotestosterone as reference, to explain the role of binding to Glu57 and Tyr91 for 5αR2 selective inhibition. Conclusion: Alignment between Hit 2 and finasteride in the binding pocket showed similar binding modes. The biological activity prediction showed antitumor and androgen targeting activity of the new hits.
Graphical abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/fmc-2023-0065
Author contributions
AA Mandour: formal analysis, investigation, methodology, visualization, original draft writing, review and editing; EB Elkaeed: supervision of original draft, review and editing; M Hagras: supervision of original draft, review and editing; HM Refaat: conceptualization, supervision of original draft, review and editing; NSM Ismail: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, visualization, supervision of original draft writing and editing.
Acknowledgements
The authors acknowledge FUE computer labs for using ChemBioDraw Ultra 14.00 (CambridgeSoft Corp., MA, USA) and Discovery Studio (DS 4.1 Biovia Discovery Studio 2016 64-bit client).
Financial disclosure
The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Availability of data & material
The data used to support the findings of the study are available from the corresponding author upon request.
Ownership
The authors declare that the submitted work is their own and that copyright has not been breached in seeking its publication.
Originality
The authors declare that the submitted work has not previously been published in full and is not being considered for publication elsewhere.