Synthesis and Cytotoxic Activity of Fingolimod (FTY720) Analogs with Various Amide Head Groups

series of 30 new analogs maintaining the backbone structure of FTY720 were synthesized by a very simple method. Regardless of newly introduced aromatic and non-aromatic head groups, the obtained structures showed cytotoxic effects. Specifically, in the case of aromatic head structures, only the head group containing nitrogen showed cytotoxic effects. In the case of non-aromatic head group, compound 23 with a relatively long chain head group showed this effect even at low concentrations. All the cytotoxic compounds showed protein phosphatase 2A activity and apoptotic effects regardless of the sphingosine kinase 1/2 inhibitory effect. Therefore, it was confirmed that the FTY720 backbone structure was an important factor that activated PP2A, resulting in anticancer effects.