Screening of amide analogues of Trichostatin A in cultures of primary rat hepatocytes: search for potent and safe HDAC inhibitors
- 98 Downloads
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
- 7.Marcos R, Monteiro RA, Rocha E (2006) Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies. Liver Int 26:116–124 doi:10.1111/j.1478-3231.2005.01201.x PubMedCrossRefGoogle Scholar