Bispyridinium cyclophanes: novel templates for human choline kinase inhibitors.
The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cyclophanes (6, 4,8-diaza-3(1,4),9(4,1)-dipyridina-1(1,4),6(1,3)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium) dibromide) has an IC(50(ChoK)) of 0.3 microM and is the most potent human ChoK inhibitor described to date.
Conejo-García
Ana
A
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, c/Campus de Cartuja s/n, 18071 Granada, Spain.
Campos
Joaquín M
JM
Sánchez-Martín
Rosario M
RM
Gallo
Miguel A
MA
Espinosa
Antonio
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C477013:4,8-diaza-3(1,4),9(4,1)-dipyridina-1(1,4),6(1,3)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium); D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D011725:Pyridines; D011726:Pyridinium Compounds; D002797:Choline Kinase