Akademik Veri Yönetim Sistemi
12th International Drug Chemistry Congress, Antalya, Türkiye, 7 - 10 Mart 2024, ss.53
Post-translational modifications of histone proteins are very important determinants of gene regulation. Histone acetylation is such a modification either induces or represses the gene expression upon acetylation and deacetylation processes, respectively. The acetyl group is removed from ε-N-acetyl lysine residues in the N-terminal tails of histones and non-histone proteins by histone deacetylases (HDACs). Since HDACs are overexpressed in cancer cells and are intriguing therapeutic targets, inhibiting them could have a positive impact on the treatment of cancer and related diseases. Class I HDAC inhibitors can be characterized by a very well-known pharmacophore that contains a zinc-binding group, linker, and cap group. HDAC inhibitors are also highly promising in the synthesis of numerous target ligands. Because computational tools reduce costs and save time, they are an essential component of today's drug design and development efforts. In this study, the design of a new series of molecules containing cinnamic acid/pyridine carboxylic acid and cinnamic acid/pyridine acetic acid hybrid molecules is presented. In the study, the cinnamic acid part (cap group) of the designed molecules was subjected to structural changes and more rigid molecules were designed. A total of 60 new molecules were designed and in silico analyses were performed. Molecular docking studies and molecular dynamics (MD) simulation analysis followed by Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) scores were calculated to predict the binding affinity of the best-scored molecule. Molecules which contain pyridine carboxylic acid zinc binding group and naphthyl cap group show the best binding scores for all HDAC Class I family enzymes, especially against HDAC3.