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Open AccessArticle

In Vitro and In Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2

1
Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany
2
Faculty of Pharmacy, Damascus University, Damascus P.O. Box 9411, Syria
3
School of Pharmacy, Faculty of Health Sciences, University of Eastern, 70211 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Athina Geronikaki
Molecules 2019, 24(7), 1380; https://doi.org/10.3390/molecules24071380
Received: 11 March 2019 / Revised: 4 April 2019 / Accepted: 5 April 2019 / Published: 8 April 2019
Protein kinase CK2 is an emerging target for therapeutic intervention in human diseases, particularly in cancer. Inhibitors of this enzyme are currently in clinical trials, indicating the druggability of human CK2. By virtual screening of the ZINC database, we found that the natural compound bikaverin can fit well in the ATP binding site of the target enzyme CK2. By further in vitro evaluation using CK2 holoenzyme, bikaverin turned to be a potent inhibitor with an IC50 value of 1.24 µM. In this work, the cell permeability of bikaverin was determined using a Caco-2 cell permeability assay as a prerequisite for cellular evaluation and the compound turned out to be cell permeable with a Papp- value of 4.46 × 10−6 cm/s. Bikaverin was tested for its effect on cell viability using a MTT assay and cell proliferation using an EdU assay in different cancer cell lines (MCF7, A427 and A431 cells). Cell viability and cell proliferation were reduced dramatically after treatment with 10 µM bikaverin for 24 h. Additionally the IncuCyte® live-cell imaging system was applied for monitoring the cytotoxicity of bikaverin in the three tested cancer cell lines. Finally, molecular dynamic studies were performed to clarify the ligand binding mode of bikaverin at the ATP binding site of CK2 and to identify the amino acids involved. View Full-Text
Keywords: antiproliferation; bikaverin; cell viability; molecular dynamics; permeability antiproliferation; bikaverin; cell viability; molecular dynamics; permeability
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MDPI and ACS Style

Haidar, S.; Aichele, D.; Birus, R.; Hielscher, J.; Laitinen, T.; Poso, A.; Jose, J. In Vitro and In Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2. Molecules 2019, 24, 1380. https://doi.org/10.3390/molecules24071380

AMA Style

Haidar S, Aichele D, Birus R, Hielscher J, Laitinen T, Poso A, Jose J. In Vitro and In Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2. Molecules. 2019; 24(7):1380. https://doi.org/10.3390/molecules24071380

Chicago/Turabian Style

Haidar, Samer; Aichele, Dagmar; Birus, Robin; Hielscher, Janine; Laitinen, Tuomo; Poso, Antti; Jose, Joachim. 2019. "In Vitro and In Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2" Molecules 24, no. 7: 1380. https://doi.org/10.3390/molecules24071380

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