Identification of apposite antagonist for androgen receptor in prostate cancer: an in silico study of fenugreek compounds

Abstract

Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from Trigonella foenum-graecum, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds’ maximum free binding energy (−103.3 ± 6, −87.4 ± 23, −68.5 ΔG_bind) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Benign prostatic cancer
• Trigonella foenum-graecum
• androgen receptor
• molecular docking
• and molecular dynamic simulations (MDS)

Acknowledgments

We wish to express our appreciation to the administration of Mols & Sims Research Institute for generously providing the essential research facilities. Additionally, we are grateful to Dr. Opeyemi Y. Omotuyi for her unwavering support and attentive care throughout the research project.

Authors’ contributions

E.A.O: Conceptualization and Validation of results. E.A.O, S.D.O and D.S.B: Software and Formal analysis. E.A.O, and O. A. A.: Data curation. E.A.O.: Writing-original draft preparation and methodology. E.A.O, E.S.O. and O.F: Writing-review and editing.

E.A.O, O.F, D.S.M, O.E.E, S.A.S, J.A.S. and O.I.O: Supervision. All authors read and approved the final manuscript for publication.

Data availability statement

The data underlying this article are available in the article and its online supplementary material.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

The study was approved by the Ethical unit of Molecular Biology and Simulation Center, Ado Ekiti, Ekiti State, Nigeria with a reference number of MSERB/CADD/NHNAS/2022/07.

Additional information

Funding

This research received no external funding.