Research Area · Protein Kinase CK2

Aurone Derivatives

A potent benzylidenebenzofuran-3(2H)-one scaffold for the development of nanomolar CK2 inhibitors.

Aurone-derived inhibitor bound within the ATP-binding cleft of protein kinase CK2

Novel CK2 inhibitors were developed within the benzylidenebenzofuran-3(2H)-one (aurone) scaffold. A series of aurone derivatives was synthesized. These compounds are structurally related to flavones and exhibit nanomolar inhibitory activity against protein kinase CK2. Structural optimization yielded several compounds with improved lipophilic efficiency. The most active compound, 12m (BFO13), displayed a CLipE value of 4.94 (CLogP = 3.5; IC50 = 3.6 nM). The binding mode of the compound within the ATP-binding site of CK2 is shown in Figure 1.

Binding mode of an aurone derivative within the ATP-binding site of protein kinase CK2
Figure 1. Binding mode of 2-(3-bromo-4-hydroxy-5-methoxybenzylidene)-5,7-dichlorobenzofuran-3-one within the ATP-binding site of CK2. The hydrogen bond is shown as a green dashed line, and hydrophobic interactions are indicated by purple dashed lines.

Publication

Protopopov MV, Vdovin VS, Starosyla SA, Borysenko IP, Prykhod'ko AO, Lukashov SS, Bilokin YV, Bdzhola VG, Yarmoluk SM. Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2. Bioorganic Chemistry. 2020;102:104062.