LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase

Eur J Med Chem. 2001 Mar;36(3):215-25. doi: 10.1016/s0223-5234(01)01219-3.

Abstract

Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutral or electron-withdrawing groups. A one-parameter regression equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect plays a critical function in the ex vivo inhibition of ChoK although the role of electrostatic interactions could be altered due to a solvation process of both ChoK and ligands.

MeSH terms

  • Choline Kinase / antagonists & inhibitors*
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Models, Molecular*
  • Pyridinium Compounds / chemical synthesis
  • Pyridinium Compounds / chemistry*
  • Pyridinium Compounds / pharmacology*
  • Spectrometry, Mass, Fast Atom Bombardment
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyridinium Compounds
  • Choline Kinase