Exploring okra-derived compounds as prospective aromatase inhibitors: a computational study for enhanced breast cancer therapy

Abstract

Estrogen receptor-positive breast cancer represents itself as the most prevalent malignancy among postmenopausal women. One of the promising therapeutic approaches involves the use of Aromatase inhibitors, which competitively bind to Aromatase, reducing estrone and estradiol levels. While current drugs have improved survival rates, they are not without adverse effects. Consequently, this study explores the computational screening of medicinally relevant compounds derived from okra (Abelmoschus esculentus) for potential Aromatase inhibition. Molecular docking employing AMDock v1.5.2 was utilized to assess binding affinities with Aromatase (PDB:3EQM). Subsequently, in-depth molecular interactions were examined using Discovery Studio Visualizer v4.5, and the stability of docked complexes was evaluated via molecular dynamics with the GROMACS package, focusing on RMSD, RMSF, H-bond count, SASA, Free energy landscape, Principal Component Analysis and binding affinity assessment. The pharmacokinetic properties of the okra compounds were predicted using admetSAR v2.0. Our findings highlight Quercetin 3-gentiobioside as a standout candidate, demonstrating superior binding affinity (-10 kcal/mol) and an estimated Ki of 46.77 nM compared to letrozole and other okra compounds. Molecular dynamic analysis confirms the stability of Quercetin 3-gentiobioside binding in terms of H-bonds and conformational integrity. In conclusion, our computational investigation identifies Quercetin 3-gentiobioside, along with Quercetin 3-O-rutinoside and Hyperin, as promising candidates for preclinical studies in the pursuit of potential Aromatase inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• Breast cancer
• aromatase inhibitors
• estrogen receptor positivity
• okra compounds
• molecular docking

Acknowledgments

The authors would like to acknowledge the Sri Ramachandra Institute of Higher Education and Research (DU) for their constant support. We also sincerely thank SCIomics, Ooty for their help in preparing the manuscript.

Disclosure statement

The authors report that there are no competing interests to declare.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.