Synthesis and biological evaluation of curcumin derivatives modified with α-amino boronic acid as proteasome inhibitors.
Synthesis and biological evaluation of curcumin derivatives modified with α-amino boronic acid as proteasome inhibitors.
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DOI：
10.1016/j.bmcl.2018.06.004
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发表时间：
2018-08
影响因子：
2.7
通讯作者：
Wenjie Zhang;Heyuan Bai;Liqiang Han;Han Zhang;Bo Xu;J. Cui;Xin Wang;Z. Ge;Runtao Li
中科院分区：
文献类型：
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作者：
Wenjie Zhang;Heyuan Bai;Liqiang Han;Han Zhang;Bo Xu;J. Cui;Xin Wang;Z. Ge;Runtao Li
姜黄素是一种广为人知的药效团，最近发现它的一些衍生物以20S蛋白酶体为靶标。在本报告中，我们设计并合成了两个系列的姜黄素衍生物，分别用不同的α-氨基硼酸进行修饰，作为有效的蛋白酶体抑制剂。结果表明，化合物II-2F的IC50值在0.17 μM~1.63 μM之间，与姜黄素相比具有更好的细胞生长抑制活性。
Curcumin is a well-known pharmacophore and some of its derivatives are shown to target 20S proteasome recently. In this report, we designed and synthesized two series of curcumin derivatives modified with different α-amino boronic acids as potent proteasome inhibitors. The synthesized compounds were evaluated for their cytotoxic activities against HCT116 cells, and the results showed that all of them exhibited excellent cell growth inhibitory activity comparing with curcumin, with the IC50values varying from 0.17 μM to 1.63 μM. CompoundII-2Fwith free boronic acid was assayed for its proteasome inhibitory activity and the results indicated thatII-2Fexhibited more potent inhibitory activity against ChT-L with high subunit selectivity than any other reported curcumin derivatives.