Design, Molecular Docking and Molecular Dynamics Simulation Studies of Novel Pyridinecarboxamide Derivatives as Potent HDAC6 inhibitors

Authors : İsmail Akçok

Pages : 165-174

View : 10 | Download : 14

Publication Date : 2025-04-30

Article Type : Research Paper

Abstract :Histone deacetylases (HDACs) are a family of enzymes which play vital roles in the regulation of gene expression and cellular processes. HDACs are classified into four main classes based on their homology, cellular localization, and structural characteristics. HDAC6 enzyme which is one of the class IIb enzyme has important functions in variety of physiological processes such as cell migration, immune responses, and neuronal function. Dysregulation of HDAC6 activity has been linked to the accumulation of toxic protein aggregates in neurodegenerative diseases, while its overexpression or altered activity in cancer cells can contribute to metastasis and tumorigenesis. In this study, potential HDAC6 inhibitors were designed and their inhibitory activities were investigated using in silico protocols, including molecular docking, molecular dynamics simulations and MM-PBSA calculations. Among the designed molecules, IA64 showed the best binding profile against HDAC6 enzyme, and could be considered as a lead molecule for further studies.
Keywords : ilaç tasarımı, kanser, HDAC6, Moleküler Kenetlenme, MD simulasyonu