title: Towards a model for the inhibition of choline kinase by a new type of inhibitor.
abstract: Bispyridinium cyclophanes are novel templates for human choline kinase inhibitors. Molecular modelling of these compounds suggests three anchorage places at the binding site of the enzyme: (i) two anionic centres of the enzyme active site separated from each other at a distance of approximately 6.2 A that bind the two positively charged nitrogen atoms; (ii) a wide hydrophobic pocket that is fulfilled by the upper linker, the benzene ring that links the two amino groups; and (iii) a smaller hydrophobic pocket that can accommodate the lower benzene ring that links both benzylic carbons. This study may be useful for the development of more potent inhibitors of the enzyme.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada 18071, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Conejo-García
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos
authors.forename: Rosario M
authors.initials: RM
authors.lastname: Sánchez-Martín
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
mesh_terms: D002797:Choline Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D002797:Choline Kinase