title: 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 48h were 0.36-0.55 microM, whereas berbamine IC(50) value was 8.9 microM. 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-kappaB 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.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Zijin Campus, Hangzhou, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Xie
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.forename: Xuzhao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Qiu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Xu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D044182:Benzylisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D044182:Benzylisoquinolines; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C027870:berbamine