title: 4,5-Diaryl imidazoles with hydroxamic acid appendages as anti-hepatoma agents.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the most abundant tumour of the liver with rising patient numbers in the Western world countries. Despite newly approved drugs like protein kinase inhibitors the survival rate is still poor.
  
  
  METHODS
  In order to identify potential new drugs for the treatment of HCC we investigated the real-time cell viability, apoptosis induction (sub-G1 cells), and HDAC (histone deacetylase) activity of two hepatocellular cancer cell lines HepG2 and Hep3B treated with new imidazole-tethered hydroxamates.
  
  
  RESULTS
  The tested cinnamyl hydroxamates exhibited significant antiproliferative and cytotoxic activity in HCC cells as apparent from high sub-G1 cell levels in flow cytometric cell cycle analyses. In Hep3B cells HDAC inhibition was observed comparable in magnitude to that induced by the clinically applied HDAC inhibitor SAHA (Zolinza, Vorinostat).
  
  
  CONCLUSIONS
  The new imidazolyl hydroxamic acids lend themselves as a possible alternative to SAHA in the therapy of HCC. Even more so since similar 4,5-diarylimidazoles lacking only the hydroxamate functionality were previously shown in animal studies to be well tolerated and orally applicable.
authors.affiliation: Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, 35043, Marburg, Germany.
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Fazio
authors.forename: Susanne
authors.initials: S
authors.lastname: Lingelbach
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy; D000077767:Panobinostat; D013449:Sulfonamides / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D013449:Sulfonamides; D000077337:Vorinostat; D000077767:Panobinostat; D006655:Histone Deacetylases; C487081:belinostat