New non-symmetrical choline kinase inhibitors

作者：Schiaffino Ortega Santiago; Carlota Lopez Cara Luisa; Rios Marco Pablo; Paz Carrasco Jimenez Maria; Gallo Miguel A; Espinosa Antonio; Marco Carmen; Entrena Antonio^*

来源：Bioorganic & Medicinal Chemistry, 2013, 21(22): 7146-7154.

DOI：10.1016/j.bmc.2013.09.003

• Choline kinase
• Inhibitors
• 3-Aminophenol
• Docking studies

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.

• 出版日期2013-11-15