Synthesis and Computational Insights of <i>p-B</i>enzoyl-Phenylalanine as Potential Estrogen Receptor Inhibitor

Abstract

Radiolabelled amino acids have been gaining great interest in medical field both as diagnostic and therapeutic agents. New pharmaceutical compound, p-benzoyl-phenylalanine (4-BP), was synthesised and investigated for its potential as estrogen receptor inhibitor for breast cancer and characterised using FT-IR, 1H and 13C-NMR spectroscopic techniques. The molecular docking study were carried out to explore the molecular interactions between 4-BP and human estrogen receptor (hERα). Docking results revealed 4-BP has high binding affinity via hydrophobic and polar-polar contacts towards hERα. Analysis of 30 ns molecular dynamics simulations results of the best docked 4-OHT and 4-BP with hERα receptor demonstrate stable complex interaction and (4-BP)-hERα undergoes less conformational fluctuations compared to the (4-OHT)-hERα. This work reports new synthesis method for 4-BP amino acid with improved anti-estrogenic properties and shed light on its interaction mechanism with hERα.