title: Screening of amide analogues of Trichostatin A in cultures of primary rat hepatocytes: search for potent and safe HDAC inhibitors.
abstract: 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.
authors.affiliation: Department of Toxicology, Vrije Universiteit Brussel, Brussels, Belgium. jfraczek@vub.ac.be
authors.forename: Joanna
authors.initials: J
authors.lastname: Fraczek
authors.forename: Sarah
authors.initials: S
authors.lastname: Deleu
authors.forename: Aneta
authors.initials: A
authors.lastname: Lukaszuk
authors.forename: Tatyana
authors.initials: T
authors.lastname: Doktorova
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.forename: Albert
authors.initials: A
authors.lastname: Geerts
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
authors.forename: Karin
authors.initials: K
authors.lastname: Vanderkerken
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; C515890:Hdac1 protein, rat; D056284:Histone Deacetylase 1