Novel NHC Precursors: Synthesis, Characterization, and Carbonic Anhydrase and Acetylcholinesterase Inhibitory Properties

Three series of imidazolidinium ligands (NHC precursors) substituted with 4‐vinylbenzyl, 2‐methyl‐1,4‐benzodioxane, and N‐propylphthalimide were synthesized. N‐Heterocyclic carbene (NHC) precursors were prepared from N‐alkylimidazoline and alkyl halides. The novel NHC precursors were characterized by 1H NMR, 13C NMR, FTIR spectroscopy, and elemental analysis techniques. The enzymes inhibition activities of the NHC precursors were investigated against the cytosolic human carbonic anhydrase I and II isoenzymes (hCA I and II) and the acetylcholinesterase (AChE) enzyme. The inhibition parameters (IC50 and Ki values) were calculated by spectrophotometric method. The inhibition constants (Ki) were found to be in the range of 166.65–635.38 nM for hCA I, 78.79–246.17 nM for hCA II, and 23.42–62.04 nM for AChE. Also, the inhibitory effects of the novel synthesized NHCs were compared to acetazolamide as a clinical CA isoenzymes inhibitor and tacrine as a clinical cholinergic enzymes inhibitor.