An azumamide C analogue without the zinc-binding functionality

TY - JOUR

T1 - An azumamide C analogue without the zinc-binding functionality

AU - Villadsen, Jesper S

AU - Kitir, Betül

AU - Wich, Kathrine

AU - Friis, Tina

AU - Madsen, Andreas Stahl

AU - Olsen, Christian Adam

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Histone deacetylase (HDAC) inhibitors have attracted considerable attention due to their promise as therapeutic agents. Most HDAC inhibitors adhere to a general "cap-linker-Zn2+-binding group" architecture but recent studies have indicated that potent inhibition may be achieved without a Zn2+-coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn2+-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.

AB - Histone deacetylase (HDAC) inhibitors have attracted considerable attention due to their promise as therapeutic agents. Most HDAC inhibitors adhere to a general "cap-linker-Zn2+-binding group" architecture but recent studies have indicated that potent inhibition may be achieved without a Zn2+-coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn2+-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.

U2 - 10.1039/c4md00252k

DO - 10.1039/c4md00252k

M3 - Journal article

SN - 2040-2503

VL - 5

SP - 1849

EP - 1855

JO - MedChemComm

JF - MedChemComm

ER -