Synthesis and applications of benzohydroxamic acid-based histone deacetylase inhibitors

Abstract This paper provides an overview of the synthesis and biological activity of the most representative benzohydroxamic acid-based histone deacetylase inhibitors published to date. Benzohydroxamic acids comprise an important class of HDAC inhibitors, and recently several of these structures have been evaluated in clinical trials for the treatment of a variety of cancers. In this overview, benzohydroxamic acids were divided in four different classes based on their reported selectivity towards zinc-dependent HDACs: a first and major class consists of HDAC6 selective inhibitors, a second class deals with pan-HDAC inhibitors, a third class comprises HDAC8 selective inhibitors and a fourth, minor class includes dual HDAC6/8 selective inhibitors. Through this approach, structure-activity relationships were identified for each class, which could help future researchers in the design and development of novel benzohydroxamic acid-based HDAC inhibitors.