Multimodal HDAC Inhibitors with Improved Anticancer Activity.
Histone deacetylases (HDACs) play a significant role in the proliferation and dissemination of cancer and represent promising epigenetic drug targets. The HDAC inhibitor vorinostat featuring a zinc-binding hydroxamate fragment was already clinically approved. However, HDAC inhibitors containing hydroxamic acids are often hampered by acquired or intrinsic drug resistance and may lead to enhanced tumor aggressiveness. In order to overcome these drawbacks of hydroxamate HDAC inhibitors, a series of multimodal derivatives of this compound class, including such with different zinc-binding groups, was recently developed and showed promising anticancer activity. This review provides an overview of the chemistry and pleiotropic anticancer modes of action of these conceptually new HDAC inhibitors.
Organic Chemistry Laboratory, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Universitatsstrasse 30, 95440 Bayreuth, Germany.
Rainer
R
Schobert
Organic Chemistry Laboratory, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Universitatsstrasse 30, 95440 Bayreuth, Germany.
Bernhard
B
Biersack
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
Anticancer drugs; DNA targeting; HDAC inhibitors; epigenetics; histone deacetylases; hybrid molecules.; kinases