The study of Li et al was the

The study of Li et al. (2009) was the first one using 7 flavonoids as CK2 holoenzyme inhibitors. Afterwards several further research groups undertook more detailed experiments to estimate the inhibitory potential of this class of inhibitors and its derivatives (Golub et al., 2011, Lolli et al., 2012). Comparing the results from our present study with the results obtained by other research groups with the CK2 holoenzyme we can see a lower inhibitory effect towards the free catalytic subunits. Some of the new inhibitors, especially chrysoeriol as well as pedalatin, tricin and scutellarin are promising start points for further chemical optimization to obtain more efficient CK2 inhibitors.
Experimental
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Introduction
CK2 and hormonal regulation of carbohydrate metabolism Metabolism is a set of chemical reactions which allow organisms to grow and reproduce, maintain their structures and respond to the environment. It is usually divided into catabolism and anabolism. These chemical reactions are organized in metabolic pathways, which are catalyzed and regulated by a sequence of different enzymes. A great number of these enzymes are regulated by reversible phosphorylation reactions. The basic metabolic pathways and components are similar in various cell species [26] and regulation of these pathways is quite similar. Carbohydrates are the most abundant biological molecules. They function in cyclic amp function storage, cellular signalling and are part of structural components. The carbohydrate metabolism and in particular glucose metabolism are mainly regulated by two hormones, insulin and glucagon. Low blood glucose triggers the release of glucagon from pancreatic α-cells, whereas, high blood glucose triggers the release of insulin from pancreatic β-cells. Transcription of the insulin gene in the β-cells of the pancreas is mainly regulated by the transcription factor Pdx1 also called IPF1, IDX1, STF1 and IUF [27]. It was recently shown that CK2 phosphorylated Pdx1 at threonine 231 and serine 232. Phosphorylation of Pdx1 by CK2 reduced the transcription factor activity of Pdx1 (Fig. 1), demonstrating that CK2 is implicated in the regulation of insulin production in pancreatic β-cells [28]. It was further shown that insulin treatment of β-cells resulted in an elevated CK2 kinase activity which down regulates insulin production. These results identified CK2 as a member of an autoregulatory pathway in pancreatic β-cells; regulating insulin production and release. This autoregulatory loop is shown in Fig. 1. Pharmacological inhibition of CK2 kinase activity with two different CK2 inhibitors resulted in an elevated insulin production and secretion. These results paved the way for CK2 to act as a target in diabetes therapy [29]. Pdx1 also regulates the transcription of the gene coding for synaptotagmin 1 which is a Ca sensor that plays a central role for insulin release in pancreatic β-cells [30]. It was shown that synaptotagmin 1 is phosphorylated by CK2 on one single site namely threonine 128. The function of the phosphorylation of synaptotagmin by CK2 awaits further examinations. Two possible functions may include binding to Ca ions and multimerization, both of which have been mapped to the vicinity of the CK2 phosphorylation site [31].