Title:In Silico Studies of Phytoconstituents to Identify Potential Inhibitors for
ERα Protein of Breast Cancer
Volume: 21
Issue: 2
Author(s): Veerachamy Alagarsamy*, Mohaideen Thasthagir Sulthana, Bandi Narendhar, Viswas Raja Solomon*, Periyasamy Parthiban, Aithamraju Satishchandra, Lalkote Aruna Jothi and Sankaranarayanan Murugesan
Affiliation:
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy - 502 294, India
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy - 502 294, India
Keywords:
ERα, breast cancer, in silico, molecular docking, ADME(T), nutraceuticals, MD analysis, drug development.
Abstract:
Background: It is noteworthy that a wide array of plants and nutraceuticals are effectively
utilized in the treatment of various cancers, demonstrating potent effects on different cancer
targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in
breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug
leads for the treatment of breast cancer.
Objective: This study aims to discover and identify the potential inhibitors against the most influential
ERα receptor by the computational approach of 134 phytochemicals from 17 medicinal plants
by using in silico docking studies.
Methods: The molecular docking was performed by a genetic algorithm using the Auto Dock Vina
program, and the validation of docking was also performed by using Molecular Dynamic (MD)
simulation by the Desmond tool of Schrödinger molecular modeling. Drug-likeness properties and
toxicity studies were conducted using SWISS PRO.
Results: The top ten highest binding energy phytochemicals ginicidin (-10.8 kcal/mol), lemairone
(-10.5 kcal/mol), ixoratannin (-10.0 kcal/mol), hydnocarpine (-9.8 kcal/mol), arabelline (-9.8
kcal/mol), acutilobine E (-9.8 kcal/mol), chaparinone (-8.9 kcal/mol), plumieride coumerate (-8.8
kcal/mol), acutilobine C (-8.7 kcal/mol), and mezerein (-8.7 kcal/mol) were taken for drug-likeness
test and ADMET profile prediction with the help of web-based server SWISS ADME and protoxII.
Docking's study dictated that ten phytochemical constituents showed greater binding interactions
than standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. MSD study was achieved
for the most active 4 phytoconstituents, and the stability of the ligand-protein complex was confirmed
and showed that all the four compounds possess comparatively stable ligand-protein complexes
with ERα target as compared to the tamoxifen-ERα complex.
Conclusion: Among the top ten phytochemicals, ginicidin (glycoside) formed a more stable complex
and had greater binding affinity than standard tamoxifen with better safety profiles. Hence,
this compound can be further studied for lead optimization and drug development for the treatment
of breast cancer.
