Advances in studies on histone deactylase inhibitors as anticancer drugs

Abstract

Inhibitors of histone deacetylases (HDIs), by affecting the process of histone acetylation, lead to changes in chromatin condensation, and in consequence, to changes in the expression of numerous genes responsible for the cell cycle and differentiation. Therefore, they can be effective in the treatment of cancer. The antitumor activity for over 15 HDIs has been confirmed so far, and some of them have been approved in the USA and Europe, mainly in combination with cytostatics or radiotherapy. For several HDIs, large clinical trials are being carried out to estimate their effectiveness, in monotherapy and new combinations. Other synthetic and natural compounds with HDI activity are tested in preclinical studies. HDIs differ in terms of chemical structure, biological activity and specificity in relation to individual HDACs. The compounds active against classic HDACs (Zn2+-dependent metalloproteins) are usually characterized by the presence the Zn2+ binding group, the linker part and the capping group. Taking into account the type of Zn2+ binding group, classic HDIs are classified as short-chain fatty acids, hydroxamic acids, cyclic peptides and benzamides. In turn, the nicotinamide adenine dinucleotide-dependent SIRTs inhibitors are small molecules, mostly nicotinamide and β-naphthol derivatives. The presented paper summarizes the most important information regarding the use of HDIs as anticancer drugs, regarding their diversified chemical structure, activity against HDACs, additional therapeutic properties and side effects. The review was made taking into account the literature from the last five years (2013-2017).