**Abstract**

The sex hormone estrogen plays critical roles in reproductive and sexual development. It regulates the expression and activity of key signaling molecules critical in various cellular signaling pathways. These signals are mediated by its binding to estrogen receptors alpha (ERα) and beta (ERβ). ERα has been shown to greatly participate in extranuclear signaling, inducing tumorogenesis and breast cancer metastasis. Small molecules from plants are reported with better selectivity toward tumorigenic cells with negligible toxicity when compared to their synthetic counterpart. The molecules used in this study were first probed for their druglikeness and their pharmacokinetic profile was elucidated before docking them to the ligand binding domain of the human ERα followed by a post docking prime analysis. All tested molecules had good drug-like and pharmacokinetic properties when compared to about 95% of orally available drugs as predicted by qikprop. The docking results revealed a strong binding interaction with ERα, influenced mostly by the vicinal diol groups of the studied molecules. These resulted in a conformational change, inducing receptor dimerization and altering the interactions of the sex hormone with other proteins. The studied ligands are promising in strongly inhibiting the binding of estrogen to ERα, thus limiting its extranuclear signaling.

**Keywords:** sex hormones, human estrogen receptor alpha (hERα), molecular docking, pharmacokinetics, extracellular signaling, breast cancer
