Repurposing statins as a potential ligand for estrogen receptor alpha via molecular docking

Abstract

Computational drug repurposing is the strategy for drug development which remarkably reduces the cost and development time. Research suggests that breast cancer development in women have been associated with cholesterol and its transporters. Cholesterol lowering drugs can be repurposed as potential therapeutic agents to prevent high cholesterol in estrogen receptor positive- breast cancer. The objective of this study was to carryout in-silico molecular docking of HMG-CoA reductase inhibitors (statins) with estrogen α receptor (3ERT) to repurpose the statins as breast cancer inhibitors. Molecular docking studies were performed to explore the mechanism of interactions between the statins and human estrogen α receptor. Docking results revealed that statins bind to the hydrophobic pocket of the estrogen α receptor with high binding affinity. The docking scores were compared with the standard drug 4- hydroxy tamoxifen. The study helped to compare the interactions amongst different statins with the receptor and the energy values produced were ranging from -8.5 to -5.5 kcal/mol. Molinspiration web servers was used to calculate the physiochemical properties and ADMET of the statins. Simvastatin showed better interaction amongst the docked statins with best protein ligand interactions, it was found to exhibit higher docking score of -8.5 kcal/mol. Therefore, we conclude that statins can be employed as an alternative drug for treatment of breast cancer.