Identification of phytochemicals from genus as estrogen receptor-α inhibitors through molecular docking, molecular dynamic simulation and DFT calculations.

Breast cancer is among the most prevalent causes of death in women worldwide. About 70-75% of these cancers are hormone-dependent, expressing estrogen receptors (ERs), mainly ER-, making it an essential target for managing breast cancer. genus has been traditionally used worldwide for its diverse biological activities, including antidiabetic, anti-inflammatory, antioxidant, etc. In the present study, phytochemicals isolated from various species of the species were evaluated for their ER- inhibitory activity through molecular docking, molecular dynamic simulation, Density Functional Theory calculations and free energy calculations. Four hundred seventy-one molecules were used through ligand preparation and docked inside the generated grid on ER- protein cavity and the standard drug tamoxifen. Fourteen molecules have shown better dock (-14.42 to -12.57 kcal/mol) scores than tamoxifen (-10.71 kcal/mol). Most of the molecules belong to the category of flavonoid glycosides. Molecules with good binding free energy (-78.81 to -12.94 kcal/mol) indicate stability inside the binding pocket. Further, based on dock score, pharmacokinetic parameters, and binding free energy, two hit molecules, and , were selected for their molecular dynamic simulation, MM/PBSA and DFT calculations for assessing their stability and structural dynamics inside the binding cavity as well as their reactivity. Through MD simulation analysis, it was evaluated that Compound could distort the protein to a greater extent. In contrast, compound was stable throughout the simulation time of 150 ns and can be further explored and studies as ER- inhibitors in breast cancer.