Heterocyclic Moieties as HDAC Inhibitors: Role in Cancer Therapeutics

'Epigenetic' regulation of genes via post-translational modulation of proteins is a well-explored approach for disease therapies, particularly cancer chemotherapeutics. Histone deacetylases (HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation, and apoptosis in tumor cells, thus leading to anticancer activity. Out of the four classes of HDAC, i.e., Class I, II, III, and IV, HDACIs act on Class IV (Zinc dependent HDAC), and various FDA-approved drugs belong to this category. The required canonical pharmacophore model (zinc-binding group, surface recognition cap, and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds exhibiting HDAC inhibitory activity, and structure-activity relationship of different synthetic derivatives reported during the last twelve years have been summarized in this review.

Automated summary

The regulation of genes through post-translational modification of proteins, known as "epigenetic" regulation, has been extensively studied for disease therapies, especially cancer chemotherapeutics. Histone deacetylases (HDACs) are important targets in epigenetic regulation and play a crucial role in balancing acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins. HDAC inhibitors (HDACIs) are biologically active compounds that have become essential for cancer treatment due to their ability to induce cell cycle arrest, differentiation, and apoptosis in tumor cells.