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

Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene 1,4-diylmetXlylene)]bis (4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium m oiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include elect ron-releasing, neutral or electron-withdrawing groups. A one-parameter regr ession equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect p lays a critical function in the ex vivo inhibition of ChoK although the rol e of electrostatic interactions could be altered due to a solvation process of both ChoK and ligands. (C) 2001 Editions scientifiques et medicales Els evier SAS.