Choline kinase inhibitory effect and antiproliferative activity of new 1,1',1"-(benzene-1,3,5-triylmethylene)tris[4-[(disubstituted)amino]pyridinium] tribromides.
Four derivatives of 1,1'-(benzene-1,3-diylmethylene)bis[4-[(disubstituted)amino]-pyridinium] dibromides (2-5) and six derivatives of 1,1',1"-(benzene-1,3,5-triylmethylene)-tris[4-[(disubstituted)amino]pyridinium] tribromides (6-11) were synthesised and examined for their inhibition of human choline kinase (ChoK) and antiproliferative activities. The latter are more potent as ChoK inhibitors than the former, but the antiproliferative activities against the HT-29 cell line show the opposite tendency. The higher affinity of the trispyridinium compared with the bispyridinium ones may be due to direct binding of the third pyridinium group to ChoK or may arise from a reduction of the unfavourable entropy of binding via an increase of the 'local concentration' of pyridinium groups.
Conejo-García
Ana
A
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Campus de Cartuja s/n, 18071 Granada, Spain.
Campos
Joaquín
J
Sánchez
Rosario M
RM
Rodríguez-González
Agustín
A
Lacal
Juan C
JC
Gallo
Miguel A
MA
Espinosa
Antonio
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001965:Bromides / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D015195:Drug Design; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001965:Bromides; D011726:Pyridinium Compounds; D002797:Choline Kinase