School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
Bioorg Med Chem. 2020 Mar 15;28(6):115347. doi: 10.1016/j.bmc.2020.115347. Epub 2020 Jan 28.
The extract of Tabebuia avellanedae has been used as a folk medicine, and the various biological activities of T. avellanedae have been extensively studied. However, few studies have reported which natural products play a role in their biological effects. In this study, we evaluated representative naphthoquinones isolated from T. avellanedae and found that furanonaphthoquinones were the key structures required to exhibit STAT3 phosphorylation inhibitory activities. Our SAR analysis indicated that removal of a hydroxyl group enhanced the STAT3 phosphorylation inhibitory activity. In addition, the combined results of a mobility shift assay, SH2 domain binding assay, and docking simulation by Autodock 4.2.6 suggested that (S)-5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione (1) could directly bind to the hinge region of STAT3.
Tabebuia avellanedae 的提取物已被用作民间药物，并且已经广泛研究了 T. avellanedae 的各种生物活性。然而，很少有研究报道哪些天然产物在其生物效应中起作用。在这项研究中，我们评估了从 Tabebuia avellanedae 中分离得到的代表性萘醌，并发现呋喃萘醌是发挥 STAT3 磷酸化抑制活性所必需的关键结构。我们的 SAR 分析表明，去除一个羟基可以增强 STAT3 磷酸化抑制活性。此外，迁移率变动分析、SH2 结构域结合分析以及 Autodock 4.2.6 的对接模拟的综合结果表明，(S)-5-羟基-2-(1-羟乙基)萘[2,3-b]呋喃-4,9-二酮（1）可以直接与 STAT3 的铰链区域结合。
