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

AKTAŞ A., Taslimi P., GÜLÇİN İ., GÖK Y.

ARCHIV DER PHARMAZIE, cilt.350, sa.6, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 350 Sayı: 6
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1002/ardp.201700045
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Acetylcholinesterase, Carbonic anhydrase, Enzyme inhibition, Enzyme purification, N-Heterocyclic carbenes, TROUT ONCORHYNCHUS-MYKISS, N-HETEROCYCLIC CARBENES, ERYTHROCYTES IN-VITRO, ISOENZYMES HCA I, ANTIOXIDANT ACTIVITY, ENZYME-ACTIVITY, ANTICHOLINERGIC PROPERTIES, MOLECULAR DOCKING, BOVINE-MILK, ISOZYMES I
  • İnönü Üniversitesi Adresli: Evet

Özet

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 H-1 NMR, C-13 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 K-i values) were calculated by spectrophotometric method. The inhibition constants (K-i) were found to be in the range of 166.65-635.38nM for hCA I, 78.79-246.17nM for hCA II, and 23.42-62.04nM 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.