Design and in silico evaluation of novel small molecule inhibitors of class I histone deacetylase enzymes

Akçok I.

5th International Eurasian Conference on Biological and Chemical Sciences, Ankara, Turkey, 23 - 25 November 2022, pp.474

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.474
  • Abdullah Gül University Affiliated: Yes


Histone deacetylases (HDACs) catalyze the removal of the acetyl group from lysine residues in the N-terminal tails ofhistones and non-histone proteins. HDACs are overexpressed in cancer cells and have been identified as remarkable drug targets, and their inhibition shows promising results in cancer and related disease therapies. Four HDAC inhibitors, vorinostat, romidepsin, belinostat, and panobinostat have been approved by the Food and Drug Administration (FDA). Class I HDAC inhibitors can be characterized by a very well-known pharmacophore that contains a zinc-binding group, linker, and cap group, and HDAC inhibitors are very useful in the development of multiple target ligands, too. Using computational tools in drug design is an inevitable part of today's drug discovery studies because it saves time and cost.

In this study, a novel compound that has an N-acyl hydrazone (NAH) scaffold was designed for targeting the Zn2+ binding site of the class I HDAC enzyme. For this purpose, molecular docking studies and molecular dynamics (MD) simulations followed by MM-PBSA (Molecular Mechanics-Poisson-Boltzmann Surface Area) were applied. Results have shown that the designed molecule could be used as a lead structure for designing new compounds for class I HDAC enzyme