QSAR of 1,1'-(1,2-ethylenebisbenzyl)bis(4-substitutedpyridinium) dibromides as choline kinase inhibitors: a different approach for antiproliferative drug design

J Campos; M C Núñez; V Rodríguez; M A Gallo; A Espinosa

doi:10.1016/s0960-894x(00)00080-9

QSAR of 1,1'-(1,2-ethylenebisbenzyl)bis(4-substitutedpyridinium) dibromides as choline kinase inhibitors: a different approach for antiproliferative drug design

Bioorg Med Chem Lett. 2000 Apr 17;10(8):767-70. doi: 10.1016/s0960-894x(00)00080-9.

Authors

J Campos¹, M C Núñez, V Rodríguez, M A Gallo, A Espinosa

Affiliation

¹ Departamento de Química Orgánica, Facultad de Farmacia, Granada, Spain.

PMID: 10782682
DOI: 10.1016/s0960-894x(00)00080-9

Abstract

Ten new structures of a series of the title compounds were synthesized and screened for their activity to inhibit choline kinase under ex vivo conditions. Their inhibitory potency correlates with the 13C chemical shifts (in CD3OD) of the methylene group bearing the positively charged nitrogen. The inhibitory effect on proliferation against the HT-29 cell line is strongly dependent on its ability to inhibit the production of phosphorylcholine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Division / drug effects
Choline Kinase / antagonists & inhibitors*
Drug Design
HT29 Cells
Humans
Magnetic Resonance Spectroscopy
Pyridinium Compounds / chemistry*
Pyridinium Compounds / pharmacology*
Spectrometry, Mass, Fast Atom Bombardment
Structure-Activity Relationship

Substances

Pyridinium Compounds
Choline Kinase