Berbamine derivatives: a novel class of compounds for anti-leukemia activity.

Abstract 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 IC 50 values at 48 h were 0.36–0.55 μM, whereas berbamine IC 50 value was 8.9 μM. 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.