Discovery of potential LXRβ agonists from Chinese herbs using molecular simulation methods.

Gang-Gang LUO; Fang LU; Lian-Sheng QIAO; Yong LI; Yan-Ling ZHANG

Return

Discovery of potential LXRβ agonists from Chinese herbs using molecular simulation methods.

Author: Gang-Gang LUO ¹ ; Fang LU ¹ ; Lian-Sheng QIAO ¹ ; Yong LI ¹ ; Yan-Ling ZHANG ¹
Author Information

1. Beijing Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Publication Type:Journal Article
Keywords: LXRβ agonists; docking; pharmacophore; traditional Chinese medicine; virtual screen
From: China Journal of Chinese Materia Medica 2016;41(16):3065-3071
CountryChina
Language:Chinese
Abstract: Liver X receptor β (LXRβ) has been a new target in the treatment of hyperlipemia, which was related to the cholesterol homeostasis. In this study, the quantitative pharmacophores were constructed by 3D-QSAR pharmacophore (Hypogen) method based on the LXRβ agonists. The optimal pharmacophore model containing one hydrogen bond acceptor, two hydrophobics and one ring aromatic was obtained based on five assessment indictors, including the correlation between predicted value and experimental value of the compounds in training set (correlation), Δcost of the models (Δcost), hit rate of active compounds (HRA), identification of effectiveness index (IEI) and comprehensive evaluation index (CAI). And the values of the five assessment indicators were 0.95, 128.65, 84.44%, 2.58 and 2.18 respectively. The best model as a query to screen the traditional Chinese medicine database (TCMD), a list of 309 compounds was obtained andwere then refined using Libdock program. Finally, based on the screening rules of the Libdock score of initial compound and the key interactions between initial compound and receptor, four compounds, demethoxycurcumin, isolicoflavonol, licochalcone E and silydianin, were selected as potential LXRβ agonists. The molecular simulation methods were high-efficiency and time-saving to obtainthe potential LXRβ agonists, which could provide assistance for further researchingnovel anti-hyperlipidemia drugs.