Novel N-propylphthalimide- and 4-vinylbenzyl-substituted benzimidazole salts: Synthesis, characterization, and determination of their metal chelating effects and inhibition profiles against acetylcholinesterase and carbonic anhydrase enzymes

J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22009. Epub 2017 Nov 17.

Abstract

The novel N-propylphthalimide-substituted and 4-vinylbenzyl-substituted N-heterocyclic carbene (NHC) precursors were synthesized by N-substituted benzimidazolium with aryl halides. The novel N-propylphthalimide-substituted and 4-vinylbenzyl-substituted NHC precursors have been characterized by using 1 H NMR, 13 C NMR, FTIR spectroscopy, and elemental analysis techniques. They were tested for the inhibition of AChE and hCA enzymes and demonstrated efficient inhibition profiles with Ki values in the range of 351.0-1269.9 nM against hCA I, 346.6-1193.1 nM against hCA II, and 19.0-76.3 nM against AChE. On the other hand, acetazolamide, a clinically used molecule, utilized as CA inhibitor, obtained a Ki value of 1246.7 nM against hCA I and 1407.6 nM against hCA II. Additionally, tacrine inhibited AChE and obtained a Ki value of 174.6 nM.

Keywords: N-heterocyclic carbene precursors; acetylcholinesterase; benzimidazole; carbonic anhydrase; metal chelating.

Publication types

  • Comparative Study

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design*
  • Humans
  • Iron Chelating Agents / chemical synthesis
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Kinetics
  • Molecular Structure
  • Nootropic Agents / chemical synthesis
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology*
  • Phthalimides / chemical synthesis
  • Phthalimides / chemistry
  • Phthalimides / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Iron Chelating Agents
  • Isoenzymes
  • Nootropic Agents
  • Phthalimides
  • Carbonic Anhydrases