Title:Computational Screening of Some Phytochemicals to Identify Best Modulators
for Ligand Binding Domain of Estrogen Receptor Alpha
Volume: 30
Issue: 20
Author(s): Veerachamy Alagarsamy*, Pottabathula Shyam Sundar, Viswas Raja Solomon*, Sankaranarayanan Murugesan, Mohammed Muzaffar-Ur-Rehman, Vishaka Sumant Kulkarni, Mohaideen Thasthagir Sulthana, Bandi Narendhar and Govindraj Sabarees
Affiliation:
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy 502 294, Gr. Hyderabad, India
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy 502 294, Gr. Hyderabad, India
Keywords:
ERα receptor, ADMET studies, molecular docking, breast cancer, phytochemicals, ayurvedic medicinal plants.
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.
