Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2

[Display omitted] •New substituted benzylidenebenzofuran-3(2H)-ones were synthesized.•41 aurones inhibited CK2 with IC50 in nanomolar range of values.•The most promising compound 12m (BFO13) has an IC50 = 3.6 nM with CLipE = 4.94. In this work, we describe the design, synthesis and SAR studies of 2-...

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Bibliographic Details
Published in:	Bioorganic chemistry Vol. 102; p. 104062
Main Authors:	Protopopov, M.V., Vdovin, V.S., Starosyla, S.A., Borysenko, I.P., Prykhod'ko, A.O., Lukashov, S.S., Bilokin, Y.V., Bdzhola, V.G., Yarmoluk, S.M.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-09-2020
Subjects:	2-benzylidenebenzofuran-3-ones Aurone Benzofurans - pharmacology Benzofurans - therapeutic use Casein Kinase II - chemistry Flavones - pharmacology Flavones - therapeutic use Humans In vitro biochemical assay Molecular docking Molecular Docking Simulation - methods Protein kinase CK2 inhibitor Structure-Activity Relationship Virtual screening Protein kinase CK2 inhibitor 2-benzylidenebenzofuran-3-ones Virtual screening Aurone In vitro biochemical assay Molecular docking
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Summary:	[Display omitted] •New substituted benzylidenebenzofuran-3(2H)-ones were synthesized.•41 aurones inhibited CK2 with IC50 in nanomolar range of values.•The most promising compound 12m (BFO13) has an IC50 = 3.6 nM with CLipE = 4.94. In this work, we describe the design, synthesis and SAR studies of 2-benzylidenebenzofuran-3-ones (aurones), a new family of potent inhibitors of CK2. A series of aurones have been synthesized. These compounds are structurally related to the synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed that 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0045-2068 1090-2120
DOI:	10.1016/j.bioorg.2020.104062