Evaluation of Zinc Chelation Ability for Non-Hydroxamic Organic Moieties

Document Type : Original Article


Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Baghdad, Iraq


Histone deacetylase (HDAC) enzymes are zinc-dependent metalloproteinases that are deregulated in a number of diseases, including cancer. The majority of the clinically used HDAC inhibitors are hydroxamates. Limitations in their clinical use due to poor selectivity, pharmacokinetics, and toxic side effects warrant the development of new inhibitors with non-hydroxamate zinc-binding groups (ZBG). Thus, in this work computational and chemical techniques were employed to assess the zinc ion chelation activity for a number of organic moieties that have potential chelation ability. Molecular modeling studies including molecular docking, molecular dynamic simulation, and ADMET experiments were conducted to evaluate the potential chelation activity of the selected organic moieties into HDAC proteins. The chosen moieties were reacted with zinc ion to explore the chelation inclination, and the resulting complexes were characterized using infrared and UV/Vis spectroscopy. According to all findings, the antipyrine (compound 1) showed a superior in silico binding data. The modeling results were supported by the experimental zinc ion chelation tendency.