IMR Press / FBL / Volume 26 / Issue 9 / DOI: 10.52586/4957
Open Access Original Research
Gas chromatography-mass spectrometry metabolic profiling, molecular simulation and dynamics of diverse phytochemicals of Punica granatum L. leaves against estrogen receptor
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1 Department of Biochemistry, Bangalore University, Bengaluru, 560029 Karnataka, India
2 DBT-BIF Facility, Department of Biotechnology, Maharani Lakshmi Ammanni College for Women, 560012 Bangalore, India
3 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada
4 Centre for Bamboo Studies, Department of Biotechnology, Bodoland University, Kokrajhar, 783370 Assam, India
5 College of Pharmacy, Prince Sattam Bin Abdulaziz University, 16278 Al-Kharj, Saudi Arabia
*Correspondence: (Sushil Kumar Middha)
Front. Biosci. (Landmark Ed) 2021, 26(9), 423–441;
Submitted: 14 January 2021 | Accepted: 19 March 2021 | Published: 30 September 2021
(This article belongs to the Special Issue Aging in animals)
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Introduction: Breast cancer is the most common type of cancer globally and its treatment with many FDA-approved synthetic drugs manifests various side effects. Alternatively, phytochemicals are natural reserves of novel drugs for cancer therapy. Punica granatum commonly known as pomegranate is a rich source of phytopharmaceuticals. Methods: The phytoconstituents of Punica granatum leaves were profiled using GC-MS/MS in the present work. Cytoscape-assisted network pharmacology of principal and prognostic biomarkers, which are immunohistochemically tested in breast cancer tissue, was carried out for the identification of protein target. Followed by, rigorous virtual screening of 145 phytoconstituents against the three ER isoforms (α, β and γ) was performed using Discovery Studio. The docked complexes were further evaluated for their flexibility and stability using GROMACS2016 through 50 ns long molecular dynamic simulations. Results: In the current study, we report the precise and systematic GC-MS/MS profiling of phytoconstituents (19 novel metabolites out of 145) of hydromethanolic extract of Punica granatum L. (pomegranate) leaves. These phytocompounds are various types of fatty acids, terpenes, heterocyclic compounds and flavonoids. 4-coumaric acid methyl ester was identified as the best inhibitor of ER isoforms with drug-likeness and no toxicity from ADMET screening. γ-ligand binding domain complex showed the best interactions with minimum RMSD, constant Rg, and the maximum number of hydrogen bonds. Conclusion: We conclude that 4-coumaric acid methyl ester exhibits favourable drug-like properties comparable to tamoxifen, an FDA-approved breast cancer drug and can be tested further in preclinical studies.

Breast cancer
MD simulations
GCMS/MS profiling
Natural compounds
Estrogen receptor
4-coumaric acid methyl ester
Fig. 1.
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