Aurone derivatives

Novel CK2 inhibitors among benzylidenebenzofuran-3(2H)-one (aurone) derivatives have been identified. A series of aurones have been synthesized. These compounds are structurally related to synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed 20 newly synthesized compounds inhibited CK2 with IC₅₀ values in the nanomolar range. Further property-based optimization of aurones was performed, yielding a series of CK2 inhibitors with enhanced lipophilic efficiency. The most potent compound 12m (BFO13) has CLipE = 4.94 (CLogP = 3.5; IC₅₀ = 3.6 nM) commensurable with the best known inhibitors of CK2. The binding mode for compounds in this class with ATP-binding site of CK2 has been proposed (Fig. 1). 

Figure 1. The binding mode of compound 2-(3-Bromo-4-hydroxy-5-methoxy-benzylidene)-5,7-dichloro-benzofuran-3-one in the CK2 active site. Hydrogen bond is shown by the green dotted line, hydrophobic interactions are presented by the magenta dotted lines.

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