title: New more polar symmetrical bipyridinic compounds: new strategy for the inhibition of choline kinase α1.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Campus de Cartuja, 18071, Granada, Spain.
authors: Francisco Fermín
authors: FF
authors: Castro-Navas
authors: Santiago
authors: S
authors: Schiaffino-Ortega
authors: María Paz
authors: MP
authors: Carrasco-Jimenez
authors: Pablo
authors: P
authors: Ríos-Marco
authors: Carmen
authors: C
authors: Marco
authors: Antonio
authors: A
authors: Espinosa
authors: Miguel Angel
authors: MA
authors: Gallo
authors: Elena
authors: E
authors: Mariotto
authors: Giuseppe
authors: G
authors: Basso
authors: Giampietro
authors: G
authors: Viola
authors: Antonio
authors: A
authors: Entrena-Guadix
authors: Luisa Carlota
authors: LC
authors: López-Cara
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002797:Choline Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003461:Crystallography; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; D011804:Quinolines; C517212:CHKA protein, human; D002797:Choline Kinase; D020169:Caspases