In Silico Study of Asparagus officinalis Plant Compounds Against Estrogen Receptor Alpha (ER-α) as a Candidate for Breast Anticancer

Abstract

Breast cancer is the most prevalent type of cancer and the leading cause of cancer-related death in women worldwide. The limitations of conventional therapies, such as the serious side effects of chemotherapy, drive the search for safer and more effective alternative treatments. Asparagus officinalis is known to contain bioactive compounds with potential anticancer properties. This study aimed to evaluate the potential of compounds from A. officinalis as oral drug candidates through an analysis of pharmaceutical feasibility based on Lipinski's Rule, pharmacokinetic and toxicity profiles, and modeling of their interaction with the estrogen receptor alpha (ER-α) using molecular docking. From 116 identified compounds, 64 satisfied Lipinski's Rule, and most showed good pharmacokinetic and toxicity profiles. The molecular docking results revealed that 19 compounds had a strong binding affinity (–7.09 to –9.59 kcal/mol). Catechin and 3PGPC showed the strongest affinity, closely approaching that of the comparative ligand, 4-hydroxytamoxifen (–9.98 kcal/mol). The interaction of these two compounds with key ER-α residues and the absence of hydrogen bonding with the His524 residue indicate that they act as antagonists against ER-α, which can inhibit the proliferation of breast cancer cells. These findings suggest that catechin and 3PGPC have the potential to be alternative ligands for ER-α and are worthy of further investigation as candidates for natural-based breast cancer drugs.