Molecular Docking Analysis of Estrogen Receptor ? to Phytochemistries in Asteraceae Family Compared to Tamoxifen in Breast Cancer

Abstract

Background:Tamoxifen is the first line hormonal therapy for Estrogen Receptor ?(ER?) breast cancer. Some of phytochemistries pose anticancer activities. However, data of those from Asteraceae family in Indonesia are lacking. The aim of this research is to know the binding affinities and binding locations of phytochemistries in Asteraceae family from Indonesia compared to tamoxifen on ER? in breast cancer.

Methods: This research wasa bioinformatic study. Subjects were3-dimensional structures ofER?, tamoxifen, and phytochemistriess Asteraceae family obtained from Indonesian HerbalDB database, Pubchem Compound, and Protein Data Bank. Subjects were prepared by Chimera 1.10 and Open Babel. Tamoxifen was docked on ER? by AutoDock Vina to know its binding affinities of ligand-receptor complex, compared to the other chosen ligands. Binding locations of ligand-reseptor were visualized by Pymol 1.7.2.

Results: The docking results showed four phytochemistriess binding affinities whichwere stronger than tamoxifen (-9.6 kcal/mol), such as lappadilactone, friedelin, benperidol, and beta-amyrin. The visualization results showed that lappadilactone, friedelin, benperidol, beta-amyrin, taraxerol, andepifriedelanol had similar binding areas totamoxifen on ER?. Lappadilactone had hydrogen bond with Tyr⁵²⁶ and benperidol had hydrogen bond with Trp³⁸³ on ER?.

Conclusions:Lappadilactone and benperidol have stronger binding affinities than tamoxifen and they have hydrogen bond with ER?, but not in active sites of ER?. Therefore, lappadilactone and benperidol may have ability to inhibit ER? activities computationally.

Keywords: Estrogen receptor ?, molecular docking, phytocemistry, tamoxifen.