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Acetoxystachybotrydial acetate, a natural compound isolated from Stachybotrys chartarum is a potent inhibitor of human protein kinase CK2
Samer Haidar * 1 , Franziska M Jürgens 2 , Dagmar Aichele 3 , Annika Jagels 4 , Hans-Ulrich Humpf 4 , Joachim Jose 1
1  Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany
2  Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Münster, Germany,
3  Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Münster, Germany, 48149
4  Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany, 48149

Published: 30 October 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5
10.3390/ECMC2019-06307
Abstract:

Human protein kinase CK2 is an emerging target for drug design. Overexpression of CK2 is closely related to many types of human cancer. It was shown that elevated levels of CK2 protect tumor cells from apoptosis [1]. Inhibition of CK2 activity can lead tumor cells into apoptosis, whereas viability of healthy cells is not affected [2]. Up till now, one ATP competitive inhibitor of CK2, silmitasertib, is in clinical trials phase II [3]. Here we report on the screening of natural compounds isolated from Stachybotrys chartarum [4]. Twelve phenylspirodrimanes and three triphenylphenols were investigated on inhibitory activity towards CK2 using a CE-based assay [5]. Triphenyl phenolestachybotrychromene C, phenylspirodrimanes stachybotrydial acetate and acetoxystachybotrydial acetate with IC50 ­values of 0.3 µM, 0.7 µM and 1.9 µM, respectively, were identified as potent CK2 inhibitors. Effect of these compounds on the proliferation of breast cancer cells MCF-7 was determined using an EdU assay. For comparison, viability of breast cancer cells MCF-7 as well as lung cancer cells A427 and epidermal cancer cells A 431 was tested using the MTT assay. In particular, acetoxystachybotrydial acetate turned out to be the most active compound. After treatment of MCF-7 cells with 1 µM for 24 h cell proliferation was blocked almost completely (99%), whereas cell viability was decreased only by 63%. Here we describe phenlyspirodrimanes as new class of CK2 inhibitors, among them acetoxystachybotrydial acetate which has proved to be the most potent representative of this series.

References

  1. Faust M, Montenarh M. Cell Tissue Res 2000; 301:329-340.
  2. Ruzzene M, Pinna LA. Biochim Biophys Acta 2010; 1804:499-504.
  3. Gowda C et al. Curr Pharm Des 2017; 23:95-107.
  4. Gratz A et al. Electrophoresis 2010; 31:634–640.
  5. Jagels A et al., Mycotoxin Res. 2018; 34: 179-185.
Keywords: CK2, natural compounds, Stachybotrys, antiproliferation
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