Villadsen, Jesper2; Kitir, Betül1; Wich, Kathrine3; Friis, Tina4; Madsen, Andreas Stahl1; Olsen, Christian Adam1
1 Department of Chemistry, Technical University of Denmark2 Organic Chemistry, Department of Chemistry, Technical University of Denmark3 University of Copenhagen4 Statens Serum Institut
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.