期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 44, 期 8, 页码 3293-3298出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2009.02.018
关键词
Berbamine derivatives; Anti-leukemia activity; Bisbenzylisoquinoline alkaloid
资金
- Program for New Century Excellent Talents in University [NCET-05-0523]
- National Natural Science Foundation of China (NSFC) [30772652, 90813026, 30672381, 30873095]
- Zhejiang Provincial program for the Cultivation of High-level Innovative Health talents
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 IC50 values at 48 h were 0.36-0.55 mu M, whereas berbamine IC50 value was 8.9 mu M. 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-kappa B 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. (C) 2008 Elsevier Masson SAS. All rights reserved.
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