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