Design, synthesis, antitumor activity, and molecular dynamics simulations of novel sphingosine kinase 2 inhibitors

[Display omitted] •Novel sphingosine kinase 2 inhibitors were designed and synthesized.•Synthesized compounds showed better enzyme inhibitory activity, anti-proliferative activity and antimigration activity.•Most compounds showed highly selective sphingosine kinase 2 inhibition.•Molecular docking studies and molecular dynamics simulations were investigated. Targeting sphingosine kinase 2 (SphK2) has become a novel strategy for the treatment of cancer. However, potent and selective SphK2 inhibitors are rare. In our work, a series of novel SphK2 inhibitors were innovatively designed, synthesized and screened. Compound 12e showed the best inhibitory activity. Molecular dynamics simulations were carried out to analyze the detailed interactions between the SphK2 and its inhibitors. Moreover, 12e exhibited anti-proliferative activity in various cancer cells, and inhibited the migration of human breast cancer cells MCF-7.