Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis.
Design, synthesis, and biological evaluation of polyphenol derivatives as DYRK1A inhibitors. The discovery of a potentially promising treatment for Multiple Sclerosis.
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DOI：
10.1016/j.bmcl.2022.128675
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发表时间：
2022-05-15
影响因子：
2.7
通讯作者：
Hwang, Yu-Wen
中科院分区：
文献类型：
--
作者：
Arald, Gian Luca;Hwang, Yu-Wen
绿茶及其天然成分因其对多种疾病的有效作用而闻名。特别是，主要儿茶素表没食子儿茶素没食子酸酯(EGCG)对双特异性酪氨酸(Y)-磷酸化调节的激酶-1A(DYRK1A)的活性已有报道；在这里，我们展示了EGCG相对于这个分子靶点的结构-活性关系(SAR)。我们研究了这四个环对其绝对几何性质及其活动性的影响。这项工作导致了更有效和更稳定的反氟儿茶素衍生物1f(IC50=35 nM)的鉴定。这种分子和一种新的给药方法在多发性硬化症(EAE)的验证模型中进行测试时，在体内显示了良好的效果。
Green tea and its natural components are known for their usefulness against a variety of diseases. In particular, the activity of main catechin Epigallocatechin gallate (EGCG) against Dual-specificity tyrosine-(Y)-phosphorylation Regulated Kinase-1A (DYRK1A) has been reported; here we are showing a structure-activity relationship (SAR) for EGCG against this molecular target. We have studied the influence of all four rings on the activity and the nature of its absolute geometry. This work has led to the identification of the more potent and stable trans fluoro-catechin derivative 1f (IC50 = 35 nM). This molecule together with a novel delivery method showed good efficacy in vivo when tested in a validated model of multiple sclerosis (EAE).
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