分子对接技术筛选黑沙蒿中黄酮类化合物的PPAR-γ激动活性成分
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篇名: 分子对接技术筛选黑沙蒿中黄酮类化合物的PPAR-γ激动活性成分
TITLE:
摘要: 目的:从黑沙蒿所含黄酮类化合物中筛选过氧化物酶体增殖物激活受体γ(PPAR-γ)的激动活性成分,为发现黑沙蒿中抗糖尿病药效物质提供参考。方法:以已知PPAR-γ激动药罗格列酮为阳性对照,采用分子对接技术对黑沙蒿中已分离得到的18个黄酮类化合物与PPAR-γ靶点进行一一分子对接,并对化合物与PPAR-γ靶点的对接亲和力、对接构象等进行分析比较,筛选黑沙蒿中可能的PPAR-γ激动活性成分。结果:有5个黄酮类化合物呈现了较好的对接亲和力,其中以化合物3(5,3′ ,4′ -三羟基-7-甲氧基黄酮)亲和力最高(-8.3 kcal/mol);对接构象分析发现,黄酮类化合物A环与B环上的氧原子易与PPAR-γ配体结合域活性位点形成1个(Tyr327)或2个(Tyr327、Arg288)氢键结合,这对于黄酮类化合物与PPAR-γ的结合以及PPAR-γ构象的稳定起着重要作用。结论:采用分子对接技术进行的虚拟筛选结果表明,黑沙蒿中的黄酮类化合物(大多含有多个自由酚羟基)易与PPAR-γ形成较好的对接模式与较高亲和力,具有潜在抗糖尿病活性;本研究可为黑沙蒿治疗2型糖尿病的化学成分研究提供参考。
ABSTRACT: OBJECTIVE: To screen the agonist active ingredients of peroxisome proliferator-activated receptor-γ (PPAR-γ) in flavonoids from Artemisia ordosica, and provide reference for finding antidiabetic agents in A. ordosica. METHODS: Using known PPAR-γ agonist rosiglitazone as positive control, molecular docking technology was conducted for docking one by one for 18 flavonoids and PPAR-γ targets obtained from A. ordosica. It was compared with binding affinities and binding modes of compounds and PPAR-γ targets, and the possible PPAR-γ agonist ingredients in A. ordosica were screened. RESULTS: 5 flavonoids showed good docking affinities, in which, compound 3 (5,3′ ,4′ -trihydroxy-7-methoxyflavone) showed the highest (-8.3 kcal/mol). Docking mode analysis showed that the phenol oxygen on ring A and ring B of the flavonoids with LBD active site of PPAR-γ formed one (Tyr327) or two hydrogen bonding (Tyr327, Arg288), which played an important role in the binding of flavonoids and PPAR-γ and the stability of PPAR-γ conformation. CONCLUSIONS: Results of virtual screening in molecular docking technology indicate that flavonoids (mostly containing multiple free phenolic hydroxyl groups) in can easily form good docking mode and high affinity with PPAR-γ, showing potential antidiabetic activity. The study can provide reference for further research of chemical ingredients for the treatment of type 2 diabetes.
期刊: 2018年第29卷第1期
作者: 肖音,肖斌,赵娜,张娜,武心亮,苏伊新
AUTHORS: XIAO Yin,XIAO Bin,ZHAO Na,ZHANG Na,WU Xinliang,SU Yixin
关键字: 黑沙蒿;分子对接技术;黄酮类化合物;过氧化物酶体增殖物激活受体-γ;亲和力;抗糖尿病
KEYWORDS: Artemisia ordosica; Molecular docking technology; Flavonoids; Peroxisome proliferator-activated receptor-γ; Af- finity; Antidiabetic
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