New more polar symmetrical bipyridinic compounds: new strategy for the inhibition of choline kinase α1.
Future Med Chem
; 7(4): 417-36, 2015.
Article
en En
| MEDLINE
| ID: mdl-25875870
ABSTRACT
AIM:
Research of the antitumor properties of biscationic compounds has received significant attention over the last few years.RESULTS:
A novel family of 1,1'-([2,2'-bipyridine]-5,5'-diylbis(methylene))bis-substituted bromide (9a-k), containing two nitrogen atoms in the linker, considered as hypothetical hydrogen bond acceptors, were synthesized and evaluated as ChoK inhibitors and their antiproliferative activity against six cancer cell lines.CONCLUSION:
The most promising compounds in this series are 1,1'-([2,2'-bipyridine]-5,5'-diylbis(methylene))bis(4-(methyl(phenyl)amino)-quinolinium bromide derivatives 9g-i (analogs to RSM932A), that significantly inhibit cancer cell growth at even submicromolar concentrations, especially against leukemia cells. Compounds 9g-i also inhibit the ChoKα1 with good or moderate values, as predicted by initial docking studies. In addition, the most active compound 9h remarkably induces apoptosis in two cell lines following the mitochondrial pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piridinas
/
Colina Quinasa
/
Inhibidores Enzimáticos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
España