Histone deacetylase (HDAC) inhibitors have attracted considerable attention due to their promise as therapeutic agents. Most HDAC inhibitors adhere to a general “ cap-linker-Zn 2+ -binding group ” architecture but recent studies have indicated that potent inhibition may be achieved without a Zn 2+ - coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn 2+ -binding group and evaluation of its inhibitory activity against recombinant human HDAC1 – 11. Furthermore, kinetic investigation of the inhibitory mechanism of both parent natural product and synthetic analogue against HDAC3-NCoR2 is reported as well as their activity against Burkitt's lymphoma cell proliferation.
Villadsen, J., Kitir, B., Wich, K., Friis, T., Madsen, A. S., & Olsen, C. A. (2014). An azumamide C analogue without the zinc-binding functionality. MedChemComm, 5, 1849-1855. https://doi.org/10.1039/C4MD00252K