Investigational New Drugs

, Volume 27, Issue 4, pp 338–346 | Cite as

Screening of amide analogues of Trichostatin A in cultures of primary rat hepatocytes: search for potent and safe HDAC inhibitors

  • Joanna FraczekEmail author
  • Sarah Deleu
  • Aneta Lukaszuk
  • Tatyana Doktorova
  • Dirk Tourwé
  • Albert Geerts
  • Tamara Vanhaecke
  • Karin Vanderkerken
  • Vera Rogiers


The vast majority of preclinical studies of HDAC inhibitors (HDAC-I) focus on the drug–target (cancer) cell interaction, whereas little attention is paid to the effects on non-target healthy cells, which could provide decisive information to eliminate potential cytotoxic compounds at a very early stage during drug development. In the current study we used cultures of primary rat hepatocytes as a read out system to select for the most potent HDAC-I in the group of structural analogues of an archetypal HDAC-I, namely Trichostatin A. This kind of approach allowed selecting compounds with high biological activity and with no apparent toxicity towards cultured hepatocytes.


Histone deacetylase inhibitors Trichostatin A Hepatotoxicity Primary rat hepatocytes 



This study was financially supported by Vrije Universiteit Brussel (OZR-VUB), Belgium through the GOA project. Part of the project is also supported by the EU FP6 project, Liintop. Thanks go to Mrs. Pauwels M., Mr. Degreef B., Mr. Branson S. and Ms. Bastiaensen E. for their technical assistance.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Joanna Fraczek
    • 1
    Email author
  • Sarah Deleu
    • 2
  • Aneta Lukaszuk
    • 3
  • Tatyana Doktorova
    • 1
  • Dirk Tourwé
    • 3
  • Albert Geerts
    • 4
  • Tamara Vanhaecke
    • 1
  • Karin Vanderkerken
    • 2
  • Vera Rogiers
    • 1
  1. 1.Department of ToxicologyVrije Universiteit BrusselBrusselsBelgium
  2. 2.Department of Hematology and ImmunologyVrije Universiteit Brussel (VUB)BrusselsBelgium
  3. 3.Department of Organic ChemistryVrije Universiteit Brussel (VUB)BrusselsBelgium
  4. 4.Department of Cell BiologyVrije Universiteit Brussel (VUB)BrusselsBelgium

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