title: Choline kinase inhibitory effect and antiproliferative activity of new 1,1',1"-(benzene-1,3,5-triylmethylene)tris[4-[(disubstituted)amino]pyridinium] tribromides.
abstract: 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.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Conejo-García
authors.forename: Joaquín
authors.initials: J
authors.lastname: Campos
authors.forename: Rosario M
authors.initials: RM
authors.lastname: Sánchez
authors.forename: Agustín
authors.initials: A
authors.lastname: Rodríguez-González
authors.forename: Juan C
authors.initials: JC
authors.lastname: Lacal
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001965:Bromides; D011726:Pyridinium Compounds; D002797:Choline Kinase