Molecular Docking
and Dynamics Simulation study for Anticancer Phytoconstituents inhibiting breast
cancer
Singh Nootan, Yadav Piyush Kumar, Singh Ajay Kumar, Gupta Divya and Gupta Garima
Res. J. Biotech.; Vol. 19(7); 40-56;
doi: https://doi.org/10.25303/1907rjbt040056; (2024)
Abstract
The main challenge in the fight against breast cancer (BC) is to create new medications
that are more selective for cancer cells and have fewer adverse effects. SPDEF (Sam
pointed domain containing ETS transcription factor) is a prostate-derived ETS factor
that maintains homeostasis, differentiation of epithelial tissues and heritable
alterations in cancer. Previously, SPDEF has been shown to be associated with BC
subtypes and is found to be down-regulated in invasive breast cancer cell lines
which is supportive of its role in tumor suppression. In the current study, SPDEF
protein was used as a potential breast cancer therapeutic target. A total of fifteen
phytoconstituents were evaluated as potential drug ligands against SPDEF using various
in silico approaches. Genistein, allicin, 2-hydroxychalcone and ajoene were free
from any of the predicted toxicological endpoints.
As per toxicological endpoints prediction study, the median lethal dosage (LD50)
values for these phytoconstituents varied from 159 to 3919 mg/Kg. Our results indicate
that out of fifteen, three phytoconstituents silibinin (-7.7 kcal/mol), codonolactone
(-6.1 kcal/mol) and genistein (-6.1 kcal/mol), showing the lowest binding energies,
had more significant inhibitory effects against SPDEF protein. We selected these
three phytoconstituents on the basis of binding scores for molecular dynamic simulations
at 200 ns to study their protein-ligand complex stability. Out of the three, silibinin-receptor
complex had more stability. The present analysis shows that silibinin could be a
potential therapeutic compound against breast cancer as assessed by its binding
interaction and stability analyses against SPDEF.
