Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors
Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors
复制标题
作为有效 RSK 抑制剂的联芳基吡啶类似物的设计、合成和抗乳腺癌评价
DOI：
10.1016/j.bmcl.2022.128565
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发表时间：
2022-01-24
影响因子：
2.7
通讯作者：
Xiao, Wei-Lie
中科院分区：
文献类型：
--
作者：
Cui, Yi-Man;Li, Wei;Xiao, Wei-Lie
为了发现和开发新型RSK激酶抑制剂，以LJH685为先导化合物，设计合成了50种吡啶联芳衍生物，并对其抗肿瘤能力进行了测试。结果表明，7d化合物抑制YB-1磷酸化的能力与LJH685相当。其中，经初步筛选，化合物7d表现出良好的抑制细胞增殖活性。因此，我们以7d为例，对其进行分子对接分析。从与LJH685的重叠组合图来看，结果验证了化合物7d与LJH685具有相似的骨架，并且与RSK具有相似的对接效果。因此，化合物7d与我们设计的RSK抑制剂相符，未来可以开发成有前景的抗肿瘤药物。
In order to discover and develop the new RSK kinase inhibitor, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of 7d compound to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among them, after preliminary screening, compound 7d showed good activity in inhibiting cell proliferation. Therefore, we took 7d as an example and performed molecular docking analysis on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound 7d has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound 7d is in line with the RSK inhibitor we designed and could be developed to a promising anti-tumor drug in the future.