Open Access

Natural chalcones as dual inhibitors of HDACs and NF-κB

  • Authors:
    • B. Orlikova
    • M. Schnekenburger
    • M. Zloh
    • F. Golais
    • M. Diederich
    • D. Tasdemir
  • View Affiliations

  • Published online on: June 15, 2012     https://doi.org/10.3892/or.2012.1870
  • Pages: 797-805
  • Copyright: © Orlikova et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Histone deacetylase enzymes (HDACs) are emerging as a promising biological target for cancer and inflammation. Using a fluorescence assay, we tested the in vitro HDAC inhibitory activity of twenty-one natural chalcones, a widespread group of natural products with well-known anti-inflammatory and antitumor effects. Since HDACs regulate the expression of the transcription factor NF-κB, we also evaluated the inhibitory potential of the compounds on NF-κB activation. Only four chalcones, isoliquiritigenin (no. 10), butein (no. 12), homobutein (no. 15) and the glycoside marein (no. 21) showed HDAC inhibitory activity with IC50 values of 60-190 µM, whereas a number of compounds inhibited TNFα-induced NF-κB activation with IC50 values in the range of 8-41 µM. Interestingly, three chalcones (nos. 10, 12 and 15) inhibited both TNFα-induced NF-κB activity and total HDAC activity of classes I, II and IV. Molecular modeling and docking studies were performed to shed light into dual activity and to draw structure-activity relationships among chalcones (nos. 1-21). To the best of our knowledge this is the first study that provides evidence for HDACs as potential drug targets for natural chalcones. The dual inhibitory potential of the selected chalcones on NF-κB and HDACs was investigated for the first time. This study demonstrates that chalcones can serve as lead compounds in the development of dual inhibitors against both targets in the treatment of inflammation and cancer.
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September 2012
Volume 28 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Orlikova B, Schnekenburger M, Zloh M, Golais F, Diederich M and Tasdemir D: Natural chalcones as dual inhibitors of HDACs and NF-κB. Oncol Rep 28: 797-805, 2012
APA
Orlikova, B., Schnekenburger, M., Zloh, M., Golais, F., Diederich, M., & Tasdemir, D. (2012). Natural chalcones as dual inhibitors of HDACs and NF-κB. Oncology Reports, 28, 797-805. https://doi.org/10.3892/or.2012.1870
MLA
Orlikova, B., Schnekenburger, M., Zloh, M., Golais, F., Diederich, M., Tasdemir, D."Natural chalcones as dual inhibitors of HDACs and NF-κB". Oncology Reports 28.3 (2012): 797-805.
Chicago
Orlikova, B., Schnekenburger, M., Zloh, M., Golais, F., Diederich, M., Tasdemir, D."Natural chalcones as dual inhibitors of HDACs and NF-κB". Oncology Reports 28, no. 3 (2012): 797-805. https://doi.org/10.3892/or.2012.1870