Target protein-oriented isolation of Hes1 dimer inhibitors using protein based methods
Target protein-oriented isolation of Hes1 dimer inhibitors using protein based methods
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DOI：
10.1038/s41598-020-58451-3
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发表时间：
2020-01-28
影响因子：
4.6
通讯作者：
Ishibashi, Masami
中科院分区：
文献类型：
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作者：
Arai, Midori A.;Morita, Kaori;Ishibashi, Masami
使用基于蛋白质的方法分离天然产物对于获得生物活性化合物具有吸引力。为了发现神经干细胞 (NSC) 分化激活剂，我们使用 Hes1-Hes1 相互作用荧光板测定从番石榴中分离出八种 Hes1 二聚体形成抑制剂，并使用 Hes1 固定珠方法从榄仁中分离出一种抑制剂。在分离的化合物中，没食子酸 (8) 和 4-O-(4''-O-没食子酰基-α-L-吡喃鼠李糖基)鞣花酸 (11) 显示出有效的 Hes1 二聚体形成抑制活性，IC50 值分别为 10.3 和 2.53 muM。化合物11剂量依赖性地加速C17.2 NSC细胞的分化活性，与对照相比增加了神经元数量125%（5μM）。
Natural products isolation using protein based methods is an attractive for obtaining bioactive compounds. To discover neural stem cell (NSC) differentiation activators, we isolated eight inhibitors of Hes1 dimer formation from Psidium guajava using the Hes1-Hes1 interaction fluorescent plate assay and one inhibitor from Terminalia chebula using the Hes1-immobilized beads method. Of the isolated compounds, gallic acid (8) and 4-O-(4 ''-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid (11) showed potent Hes1 dimer formation inhibitory activity, with IC50 values of 10.3 and 2.53 mu M, respectively. Compound 11 accelerated the differentiation activity of C17.2 NSC cells dose dependently, increasing the number of neurons with a 125% increase (5 mu M) compared to the control.