Heterocyclic Moieties as HDAC Inhibitors: Role in Cancer Therapeutic

Abstract

Abstract: ‘Epigenetic’ regulation of genes via post-translational modulation of proteins is a well explored approach for the 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 an important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation and apoptosis in tumor cells and thus leads 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 last twelve years have been summarized in this review.