Synthesis, characterization, crystal structure, alpha-glycosidase, and acetylcholinesterase inhibitory properties of 1,3-disubstituted benzimidazolium salts


BAL S., Demirci O., ŞEN B., Taslimi P., AKTAŞ A., GÖK Y., ...More

ARCHIV DER PHARMAZIE, vol.354, no.5, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 354 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1002/ardp.202000422
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: acetylcholinesterase, alpha-glycosidase, benzimidazolium salts, crystal structure, fluorobenzyl substituted, CARBONIC-ANHYDRASE INHIBITION, COMPLEXES SYNTHESIS, CATALYTIC-ACTIVITY, DIRECT ARYLATION, PRECURSORS SYNTHESIS, ANTICANCER ACTIVITY, CARBENE PRECURSORS, MIZOROKI-HECK, 1ST SYNTHESIS, BUTYRYLCHOLINESTERASE
  • Inonu University Affiliated: Yes

Abstract

Chloro-/fluorobenzyl-substituted benzimidazolium salts were synthesized from the reaction of 4-fluorobenzyl/2-chloro-4-fluorobenzyl-substituted benzimidazole and chlorinated aromatic hydrocarbons. They were characterized using various spectroscopic techniques (Fourier-transform infrared and nuclear magnetic resonance) and elemental analysis. In addition, the crystal structures of the complexes 1a -d and 2b were determined by single-crystal X-ray diffraction methods. These compounds were crystallized in the triclinic crystal system with a P-1 space group. The crystal packing of all complexes is dominated by O-HMIDLINE HORIZONTAL ELLIPSISCl hydrogen bonds, which link the water molecules and chloride anions, forming a chloride-water tetrameric cluster. These synthesized salts were found to be effective inhibitors for alpha-glycosidase and acetylcholinesterase (AChE), with K-i values ranging from 45.77 +/- 6.83 to 102.61 +/- 11.56 mu M for alpha-glycosidase and 0.94 +/- 0.14 to 10.24 +/- 1.58 mu M for AChE. AChE converts acetylcholine into choline and acetic acid, thus causing the return of a cholinergic neuron to its resting state. Discovering AChE and alpha-glycosidase inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease and diabetes.