In silico estrogen receptor alpha antagonist studies and toxicity prediction of Melia azedarach leaves bioactive ethyl acetate fraction

Abstract

The estrogen hormone dependent accounts for a major cause in the incidence of women breast cancer. Thus, their receptor, especially the estrogen receptor α (ER-α), is becoming a target in endocrine treatment. These ligand-inducible nuclear functions are regulated by an array of phytochemical and synthetic compounds, such as 17 β-estradiol and tamoxifen (4-hydroxytamoxifen [4OHT]). The Chinaberry (<i>Melia azedarach</i>) leaves are known naturally for relieving internal and external diseases. Previous studies revealed the potency of <i>Melia</i>'s ethanolic extract and ethyl acetate fractions as anticancer; furthermore, this study aimed to resolve possible ER-α antagonist's mechanism and safety from <i>M. azedarach</i> leaves ethyl acetate fraction contents. <i>Melia</i>'s phytochemical content was analyzed with electrospray ionization liquid chromatography-mass spectrometry, while its ER-α antagonist's potency was investigated by <i>in silico</i>. The computational docking was used to 3ERT (a human ER-α-4OHT binding domain complex) with Autodock Vina and related programs. The results presented Energy binding (ΔG) of <i>Melia</i>'s quercetin 3-<i>O</i>-(2'',6''-digalloyl)-β-<i>D</i>-galactopyranoside was similar to 4OHT, and lower than its agonist 17 β-estradiol. Furthermore, the toxicity prediction of these compounds were revealed safer than 4OHT. The <i>Melia</i>'s leaves ethyl acetate fraction, therefore, is a potential pharmacological material for further studies.