Influence of the linker in bispyridium compounds on the inhibition of human choline kinase.
Studies have been aimed to establish the structure-activity relationship that define choline kinase (ChoK) inhibitory potency and antiproliferative activity of a set of 25 bispyridinium compounds with electron-releasing groups at position 4. Here we report that, according to their inhibitory activities against human ChoK, the enzymatic inhibitory potency is closely related to the size of the linker, the 3,3'-biphenyl moiety being the most suitable. The N-methylanilino and its derivatives, 4-chloro-N-methylanilino and 3,5-dichloro-N-methylanilino, render higher ChoK inhibitory and antiproliferative activities against the HT-29 human colon cancer cell line.
Departamento de Quimica Farmaceutica y Organica, Facultad de Farmacia, Universidad de Grenada, Campus de Cartuja s/n, 18071 Granada, Spain.
Ana
A
Conejo-García
Mónica
M
Báñez-Coronel
Rosario M
RM
Sánchez-Martín
Agustín
A
Rodríguez-González
Angeles
A
Ramos
Ana
A
Ramírez de Molina
Antonio
A
Espinosa
Miguel Angel
MA
Gallo
Joaquín M
JM
Campos
Juan Carlos
JC
Lacal
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D001713:Biphenyl Compounds; D003521:Cyclopropanes; D011726:Pyridinium Compounds; D002797:Choline Kinase