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

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Martha Ervina, Mohammad Pratama, Hadi Poerwono, Juni Ekowati, Retno Widyowati, Katsuyoshi Matsunami, Sukardiman

2021 Journal of Advanced Pharmaceutical Technology and Research Vol. 12 Issue 3 Article Cited by 14 Quartile

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 (Melia azedarach) leaves are known naturally for relieving internal and external diseases. Previous studies revealed the potency of Melia's ethanolic extract and ethyl acetate fractions as anticancer; furthermore, this study aimed to resolve possible ER-α antagonist's mechanism and safety from M. azedarach leaves ethyl acetate fraction contents. Melia's phytochemical content was analyzed with electrospray ionization liquid chromatography-mass spectrometry, while its ER-α antagonist's potency was investigated by in silico. 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 Melia's quercetin 3-O-(2'',6''-digalloyl)-β-D-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 Melia's leaves ethyl acetate fraction, therefore, is a potential pharmacological material for further studies. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.

Affiliations

Doctoral Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Indonesia; Department of Pharmaceutical Biology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, Indonesia; Department of Pharmacy, Faculty of Health Sciences, Universitas Muhammadiyah Palangkaraya, Palangka Raya, Indonesia; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia; Department of Pharmacognosy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Higashihiroshima, Japan