Discovery, biological activity, synthesis and potential therapeutic utility of naturally occurring histone deacetylase inhibitors

A number of small-molecule natural products have been shown to inhibit the activity of histone deacetylases (HDACs). These enzymes catalyze the hydrolysis of N-acetyl lysine residues of the histone proteins that package chromosomal DNA and thereby play a vital role in mediating gene expression. HDAC inhibitors (HDACi) are potent cytotoxic agents with significant potential as anticancer therapeutics and it is currently thought that their selective activity on members of specific subclasses of the eighteen known human HDAC isoforms is important to this activity and to moderation of their toxicity. Herein, we discuss both linear and cyclic HDACi, as well as selected synthetically derived analogs.