New non-symmetrical choline kinase inhibitors.
Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. Choline kinase (ChoK) is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine (PC), the major phospholipid in eukaryotic cell membranes. In the present paper, a new family of non-symmetrical monocationic compounds is developed including a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. The most promising compounds in these series as ChoK inhibitors are 3f and 4f, while compounds 3c, 3d and 4c are the better antiproliferative agents. The analysis of the biological data observed in the described series of compounds mays represents a platform for the design of more active molecules.
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Campus de Cartuja s/n, Universidad de Granada,18071 Granada, Spain.
Santiago
S
Schiaffino-Ortega
Luisa Carlota
LC
López-Cara
Pablo
P
Ríos-Marco
Maria Paz
MP
Carrasco-Jimenez
Miguel A
MA
Gallo
Antonio
A
Espinosa
Carmen
C
Marco
Antonio
A
Entrena
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002797:Choline Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006426:Hemicholinium 3 / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006426:Hemicholinium 3; D002797:Choline Kinase
3-Aminophenol; Choline kinase; Docking studies; Inhibitors