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

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-H⋯Cl 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 α-glycosidase and acetylcholinesterase (AChE), with K_i values ranging from 45.77 ± 6.83 to 102.61 ± 11.56 µM for α-glycosidase and 0.94 ± 0.14 to 10.24 ± 1.58 µM 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 α-glycosidase inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease and diabetes.

Keywords: acetylcholinesterase; benzimidazolium salts; crystal structure; fluorobenzyl substituted; α-glycosidase.