Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 7;23(18):4403-4408.
doi: 10.1039/d5ob00310e.

Semisynthesis of bersavine and berbamine derivatives that target the CaMKIIγ:cMyc axis for lymphoma therapy

Berkley Lujan  1 , Mingfeng Zhang  2 , Yujie Cao  1 , Arnav Kacker  1 , Lina Mai  1 , Shunquan Wu  2 , Taylor Alexander  1   3 , Wendong Huang  2 , Kevin G M Kou  1
Affiliations

Semisynthesis of bersavine and berbamine derivatives that target the CaMKIIγ:cMyc axis for lymphoma therapy

Berkley Lujan et al. Org Biomol Chem. .

Abstract

Berbamine, a bisbenzylisoquinoline alkaloid (bisBIA), is a promising lead for developing novel therapeutics to treat aggressive cancers such as lymphoma, by targeting the CaMKIIγ:cMyc axis. Herein, we report an aza-Friedel-Crafts method for ortho-aminoalkylation of berbamine's phenolic motif, enabling the semisynthesis of the natural product bersavine and analogs that complement current methods focusing on modifying the phenolic oxygen. Several new analogs synthesized by this method exhibit potent cytotoxicity against lymphoma-associated cell line H9 exceeding the naturally occurring berbamine (1) and bersavine (3a). A molecular docking analysis was used to devise a model that rationalizes the structure-activity relationship between the novel bisBIA analogs and CaMKIIγ inhibition.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

The authors declare that the novel CaMKIIγ inhibitors described in this study is included in a provisional patent that is jointly owned by the authors, the University of California, Riverside (UCR), and The City of Hope National Medical Center (COH). The potential financial interest in the patent does not affect the integrity or objectivity of the research. All research findings and conclusions are independent of any financial and intellectual property considerations.

Similar articles

See all similar articles

References

    1. Miller DM, Thomas SD, Islam A, Muench D, Sedoris K, Clin. Cancer Res 2012, 18, 5546. - PMC - PubMed
    1. Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE, Chang AN, Frazier J, Chau BN, Loboda A, Linsley PS, Cleary MA, Park JR, Grandori C, Proc. Natl. Acad. Sci. U. S. A 2012, 109, 9545. - PMC - PubMed
    1. Gu Y, Chen T, Meng Z, Gan Y, Xu X, Lou G, Li H, Gan X, Zhou H, Tang J, Xu G, Huang L, Zhang X, Fang Y, Wang K, Zheng S, Huang W, Xu R, Blood 2012, 120, 4829. - PMC - PubMed
    1. Gu Y, Zhang J, Ma X, Kim B.-w., Wang H, Li J, Pan Y, Xu Y, Ding L, Yang L, Guo C, Wu X, Wu J, Wu K, Gan X, Li G, Li L, Forman SJ, Chan WC, Xu R, Huang W, Cancer Cell 2017, 32, 115.e7; - PMC - PubMed
    2. Liu X, Xu S, Zhang J, Fan M, Xie J, Zhang B, Li H, Yu G, Liu Y, Zhang Y, Song J, Horne D, Chan WC, Chu X, Huang W, Hematol. Oncol 2022, 40, 356. - PMC - PubMed
    1. Nassal D, Gratz D, Hund TJ, Front. Pharmacol 2020, 11, 35. - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources