Design, synthesis and biological evaluation of new embelin derivatives as CK2 inhibitors.

A new series of furan embelin derivatives was synthesized and characterized as ATP-competitive CK2 inhibitors. The new compounds were efficiently synthesized using a multicomponent approach from embelin (1), aldehydes and isonitriles through a Knoevenagel condensation/Michael addition/heterocyclization. Several compounds with inhibitory activities in the low micromolar or even submicromolar were identified. The most active derivative was compound 4l (2-(tert-butylamino)-3-(furan-3-yl)-5-hydroxy-6-undecylbenzofuran-4,7-dione) with an IC value of 0.63 μM. It turned out to be an ATP competitive CK2 inhibitor with a K value determined to be 0.48 μM. Docking studies allowed the identification of key ligand-CK2 interactions, which could help to further optimize this family of compounds as CK2 inhibitors.