Glycine-Conjugated α-Mangostins as Potential Estrogen Receptor Alpha (ERα) Antagonists through Pharmacophore Modeling, Docking Analysis, and Molecular Dynamics Simulations

Abstract

Natural compounds have demonstrated good biological activity when combined with certain amino acids. For example, a glycine-conjugated glycyrrhetinic acid exhibits heightened efficiency against MCF7 cancer cells. Consequently, a molecular modeling analysis is conducted to construct glycine-conjugated α-mangostins and investigate their potential. According to pharmacophore modeling using the ligand-based drug design technique, only two glycine-conjugated α-mangostins conform to the pharmacophore features. The docking simulation results show that the Am1Gly conjugate can interact with the estrogen receptor-α (ERα) with a binding energy of −10.91 kcal/mol. This interaction is further supported by molecular dynamics simulations performed over a 200 ns timeframe. Based on molecular dynamics modeling using the MMPBSA method, the binding affinity of Am1Gly (ΔGTotal = −48.79 kcal/mol) is determined. The results of this analysis indicate that Am1Gly might function as an antagonist to estrogen receptors.

Keywords

• α-mangostin
• amino acids
• pharmacophore
• molecular docking
• molecular dynamics