In Silico Approaches for the Identification of Novel Inhibitors against Breast Cancer Up-Regulated Protein

Breast cancer is a type of cancer that develops in the breast tissues. When some breast cells begin to grow abnormally, breast cancer develops. These cells grow and divide at a faster rate than healthy cells and continue to grow, generating a lump or mass. Cancer cells in the breast may spread to lymph nodes or other places of the body. The hormone estrogen encourages cancer growth when it binds to the receptor of the targeted protein. The purpose of this study is the rational screening of a 15,000 phytochemicals library against the estrogen receptor alpha protein. The library was employed for molecular docking to find the binding affinities and simulation analysis of the top-selected compounds. The top four compounds, Mangostenone E, Exiguaflavanone M, Sanggenon A, and Flaccidine were identified as direct inhibitors of estrogen receptors as evident from their high binding affinity and occupancy of specific binding sites. Mangostenone E was the leading phytochemical that showed a high docking score—15.97 (kcal/mol)—and bonding interaction at the active site of Mangostenone E. Leading phytochemicals were subjected to analysis for drug-like properties that further reinforced their validation. Potential molecules identified in this study can be considered lead drugs for the treatment of breast cancer. KEYWORDS Bioinformatics, docking, drug candidates, molecular dynamic simulation, phytochemicals, protein data bank