Berbamine derivatives: a novel class of compounds for anti-leukemia activity.
Berbamine derivatives: a novel class of compounds for anti-leukemia activity.
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DOI：
10.1016/j.ejmech.2009.02.018
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发表时间：
2009-08
影响因子：
6.7
通讯作者：
Jinwen Xie;Tingxuan Ma;Y. Gu;Xuzhao Zhang;X. Qiu;Lei Zhang;R. Xu;Yongping Yu
中科院分区：
文献类型：
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作者：
Jinwen Xie;Tingxuan Ma;Y. Gu;Xuzhao Zhang;X. Qiu;Lei Zhang;R. Xu;Yongping Yu
我们的前期研究表明，从中药小檗中提取的天然化合物小檗胺选择性地诱导来自K562细胞系和CML患者的表达伊马替尼（IM）的Bcr/Bcr的白血病细胞凋亡。本文合成了一系列新的小檗胺衍生物。化合物2 e、2g、3f、3 k、3q和3u对伊马替尼耐药的K562白血病细胞表现出一致的高抗肿瘤活性。48 h的IC_（50）值为0.36-0.55μM，小檗胺的IC_（50）值为8.9μM。细胞周期分析结果显示化合物3 h可使G 0/G1期细胞减少。特别地，这些化合物显示出对NF-κB p65的胞质至核易位的有效抑制，NF-κB p65在白血病干细胞的存活中起关键作用。这些结果表明，小檗胺可能是一个很好的起点，为开发新的先导化合物，在打击白血病。
Our previous studies showed that the natural compound berbamine, from Chinese herb Berberis amurensis, selectively induces apoptosis of imatinib (IM)-resistant-Bcr/Abl-expressing leukemia cells from the K562 cell line and CML patients. Here, a series of new berbamine derivatives were obtained by synthesis. In this series, high to very high activity in vitro has been found. Compounds 2e, 2g, 3f, 3k, 3q and 3u exhibited consistent high anti-tumor activity for imatinib-resistant K562 leukemia cells. Their IC50values at 48h were 0.36–0.55μM, whereas berbamine IC50value was 8.9μM. Cell cycle analysis results showed that compound 3h could reduce G0/G1 cells. In particular, these compounds displayed potent inhibition of the cytoplasm-to-nucleus translocation of NF-κB p65 which plays a critical role in the survival of leukemia stem cells. These results suggest that berbamine could be a good starting point for the development of novel lead compounds in the fight against leukemia.