基于黄酮的启发，发现了苯亚甲基苯并呋喃-3(2H)-酮（苯并呋喃酮）作为人蛋白激酶 CK2 的有效抑制剂。
Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2.
机构信息
Institute of Molecular Biology and Genetics, NAS of Ukraine, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
Institute of Molecular Biology and Genetics, NAS of Ukraine, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
出版信息
Bioorg Chem. 2020 Sep;102:104062. doi: 10.1016/j.bioorg.2020.104062. Epub 2020 Jun 30.
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 IC 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; IC = 3.6 nM) commensurable with the best known inhibitors of CK2.
在这项工作中，我们描述了 2-苄基亚基苯并呋喃-3-酮（aurones）的设计、合成和 SAR 研究，这是一类新型强效 CK2 抑制剂。我们已经合成了一系列 aurones。这些化合物与合成黄酮类化合物在结构上具有相关性，并对 CK2 表现出纳摩尔级的活性。生化测试表明，20 种新合成的化合物以纳摩尔级的 IC 值抑制 CK2。我们对 aurones 进行了进一步的基于特性的优化，得到了一系列具有增强脂溶性效率的 CK2 抑制剂。最有效的化合物 12m（BFO13）具有 CLipE=4.94（CLogP=3.5；IC=3.6 nM），与最知名的 CK2 抑制剂相当。
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