Investigational New Drugs

, Volume 27, Issue 4, pp 338–346

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

  • Joanna Fraczek
  • Sarah Deleu
  • Aneta Lukaszuk
  • Tatyana Doktorova
  • Dirk Tourwé
  • Albert Geerts
  • Tamara Vanhaecke
  • Karin Vanderkerken
  • Vera Rogiers
PRECLINICAL STUDIES

DOI: 10.1007/s10637-008-9180-x

Cite this article as:
Fraczek, J., Deleu, S., Lukaszuk, A. et al. Invest New Drugs (2009) 27: 338. doi:10.1007/s10637-008-9180-x

Summary

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.

Keywords

Histone deacetylase inhibitorsTrichostatin AHepatotoxicityPrimary rat hepatocytes

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Joanna Fraczek
    • 1
  • 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