Title:Multimodal HDAC Inhibitors with Improved Anticancer Activity
Volume: 18
Issue: 1
Author(s): Rainer Schobert and Bernhard Biersack*
Affiliation:
- Organic Chemistry Laboratory, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Universitatsstrasse 30, 95440 Bayreuth,Germany
Keywords:
Anticancer drugs, epigenetics, histone deacetylases, kinases, DNA targeting, HDAC inhibitors, hybrid molecules.
Abstract: 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.
