Computational Screening of Some Phytochemicals to Identify Best Modulators for Ligand Binding Domain of Estrogen Receptor Alpha
- Authors: Alagarsamy V.1, Sundar P.2, Solomon V.1, Murugesan S.3, Muzaffar-Ur-Rehman M.4, Kulkarni V.1, Sulthana M.1, Narendhar B.1, Sabarees G.5
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Affiliations:
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
- Department of Pharmaceutical Chemistry, Vasantidevi Patil Institute of Pharmacy
- Department of Pharmacy, BITS Pilani
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani
- Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology,
- Issue: Vol 30, No 20 (2024)
- Pages: 1599-1609
- Section: Immunology, Inflammation & Allergy
- URL: https://vestnikugrasu.org/1381-6128/article/view/645764
- DOI: https://doi.org/10.2174/0113816128287431240408045732
- ID: 645764
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Abstract
Objective:The peculiar aim of this study is to discover and identify the most effective and potential inhibitors against the most influential target ERα receptor by in silico studies of 45 phytochemicals from six diverse ayurvedic medicinal plants.
Methods:The molecular docking investigation was carried out by the genetic algorithm program of AutoDock Vina. The molecular dynamic (MD) simulation investigations were conducted using the Desmond tool of Schrödinger molecular modelling. This study identified the top ten highest binding energy phytochemicals that were taken for drug-likeness test and ADMET profile prediction with the help of the web-based server QikpropADME.
Results:Molecular docking study revealed that ellagic acid (-9.3 kcal/mol), emodin (-9.1 kcal/mol), rhein (-9.1 kcal/mol), andquercetin (-9.0 kcal/mol) phytochemicals showed similar binding affinity as standard tamoxifen towards the target protein ERα. MD studies showed that all four compounds possess comparatively stable ligand-protein complexes with ERα target compared to the tamoxifen-ERα complex. Among the four compounds, phytochemical rhein formed a more stable complex than standard tamoxifen. ADMET studies for the top ten highest binding energy phytochemicals showed a better safety profile.
Conclusion:Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for treating breast cancer, according to the notion of drug repurposing. Hence, these phytochemicals can be further studied and used as a parent core molecule to develop innovative lead molecules for breast cancer therapy.
About the authors
Veerachamy Alagarsamy
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
Author for correspondence.
Email: info@benthamscience.net
Pottabathula Sundar
Department of Pharmaceutical Chemistry, Vasantidevi Patil Institute of Pharmacy
Email: info@benthamscience.net
Viswas Solomon
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
Author for correspondence.
Email: info@benthamscience.net
Sankaranarayanan Murugesan
Department of Pharmacy, BITS Pilani
Email: info@benthamscience.net
Mohammed Muzaffar-Ur-Rehman
Department of Pharmacy, Birla Institute of Technology and Science, Pilani
Email: info@benthamscience.net
Vishaka Kulkarni
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
Email: info@benthamscience.net
Mohaideen Sulthana
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
Email: info@benthamscience.net
Bandi Narendhar
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy
Email: info@benthamscience.net
Govindraj Sabarees
Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology,
Email: info@benthamscience.net
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