Natural products as zinc-dependent histone deacetylase inhibitors

Zinc-dependent histone deacetylases (HDACs), a family of hydrolases that remove acetyl groups from lysine residues, play an important role in the regulation of multiple processes, from gene expression to protein activity. The dysregulation of HDACs is associated with many diseases including cancer, neurological disorders, cellular metabolism disorders, and inflammation. Molecules that act as HDAC inhibitors (HDACi) exhibit a variety of related bioactivities. In particular, HDACi have been applied clinically for the treatment of cancers. Inhibition through competitive binding of the catalytic domain of these enzymes has been achieved by a diverse array of small-molecule chemotypes, including a number of natural products. This review provides a systematic introduction of natural HDACi, with an emphasis on their enzyme inhibitory potency, selectivity, and biological activities, highlighting their various binding modes with HDACs.