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In Silico and In Vitro Studies of Natural Compounds as Human CK2 Inhibitors
Current Computer-Aided Drug Design ( IF 1.7 ) Pub Date : 2021-03-31 , DOI: 10.2174/1573409916666200311150744
Samer Haidar 1 , Franziska Jürgens 1 , Dagmar Aichele 1 , Joachim Jose 1
Affiliation  

Background: Casein Kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase with broad spectrum of substrates. This enzyme is widely expressed in eukaryotic cells and is overexpressed in different human cancers. Thus, the inhibition of CK2 can induce the physiological process of apoptosis leading to tumor cell death.

Objectives: Selecting natural inhibitors toward the target enzyme using database mining.

Methods: With our continuous effort to discover new compounds with CK2 inhibitory effect, several commercial natural databases were searched using molecular modeling approach and the selected compounds were evaluated in vitro.

Results: Three compounds were selected as candidates and evaluated in vitro using CK2 holoenzyme, their effect on three cancer cell lines was determined. The selected candidates were weak inhibitors toward the target enzyme, only one compound showed moderate effect on cell viability.

Conclusion: Several natural databases were screened, compounds were selected and tested in vitro. Despite the unexpected low inhibitory activity of the tested compounds, this study can help in directing the search of potent CK2 inhibitors and better understand the binding requirements of the ATP competitive inhibitors.



中文翻译:

天然化合物作为人类 CK2 抑制剂的计算机模拟和体外研究

背景:酪蛋白激酶 2 (CK2) 是一种普遍存在的细胞丝氨酸-苏氨酸激酶,具有广谱底物。这种酶在真核细胞中广泛表达,并在不同的人类癌症中过度表达。因此,CK2的抑制可以诱导细胞凋亡导致肿瘤细胞死亡的生理过程。

目标:使用数据库挖掘选择针对目标酶的天然抑制剂。

方法:随着我们不断努力发现具有 CK2 抑制作用的新化合物,使用分子建模方法搜索了几个商业天然数据库,并对选定的化合物进行了体外评估。

结果:选择三种化合物作为候选化合物,并使用 CK2 全酶进行体外评估,确定它们对三种癌细胞系的影响。选定的候选物是针对目标酶的弱抑制剂,只有一种化合物对细胞活力表现出中等影响。

结论:筛选了几个天然数据库,选择了化合物并进行了体外测试。尽管所测试化合物的抑制活性出乎意料地低,但这项研究有助于指导寻找有效的 CK2 抑制剂并更好地了解 ATP 竞争性抑制剂的结合要求。

更新日期:2021-05-18
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