In silico identification of newly designed potent class I and class IIb histone deacetylase enzyme inhibitors

6th International Eurasian Conference on Biological and Chemical Sciences (EurasianBioChem 2023), Ankara, Türkiye, 11 - 13 Ekim 2023, ss.427

There are a lot of studies that show dysregulation of histone deacetylases (HDACs) is related to cancer

development and progression. HDAC enzymes catalyze the removal of the acetyl group from lysine residues

in the N-terminal tails of histones and non-histone proteins. HDACs are fascinating therapeutic targets because

they are overexpressed in cancer cells, and their inhibition offers hope for the treatment of cancer and other

diseases related to them. Because of this relation between HDACs and development of cancer, scientists have

been quite interested in HDACs as a target to battle against cancer. Four HDAC inhibitors, vorinostat,

romidepsin, belinostat, and panobinostat have been approved by the Food and Drug Administration (FDA) so

far. In this study, a series of novel compounds that contains hydroxamic acid Zn2+ binding group, N-acyl

hydrazone linker, and pyrrolopyrimidine or purine cap region were designed for targeting class I and class IIb

HDAC enzymes (Figure 1). Through the use of molecular docking studies and molecular dynamics (MD)

simulation analysis, the potential interactions between ligands and enzymes were revealed. Molecular

Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) scores were calculated to predict the binding

affinity.