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-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.
Campos
J
J
Departamento de Química Orgánica, Facultad de Farmacia, Campus de Cartuja s/n, E-18071, Granada, Spain.
del Carmen Núñez
M
M
Rodríguez
V
V
Entrena
A
A
Hernández-Alcoceba
R
R
Fernández
F
F
Lacal
J C
JC
Gallo
M A
MA
Espinosa
A
A
D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds; D002797:Choline Kinase