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.