Molecular Docking and Dynamics Simulation study for Anticancer Phytoconstituents inhibiting breast cancer

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.