Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as apotential drug targeting breast cancer: Investigations through computational, molecular docking andconceptual DFT studies

Abstract

Breast cancer is the second most common malignancy infemales worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simu lations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWKand 2WTT)with theselected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. Themolecular docking result showed that among 44 compounds, two of them, Ashwagand hanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid-dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) andp73tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution