Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group

Tom Y H Wu; Christian Hassig; Yiqin Wu; Sheng Ding; Peter G Schultz

doi:10.1016/j.bmcl.2003.10.055

Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group

Bioorg Med Chem Lett. 2004 Jan 19;14(2):449-53. doi: 10.1016/j.bmcl.2003.10.055.

Authors

Tom Y H Wu¹, Christian Hassig, Yiqin Wu, Sheng Ding, Peter G Schultz

Affiliation

¹ Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.

PMID: 14698179
DOI: 10.1016/j.bmcl.2003.10.055

Abstract

Histone deacetylases (HDAC) are promising targets for cancer chemotherapy. HDAC inhibitors are thought to act in part by disrupting normal cell cycle regulation, resulting in apoptosis and/or differentiation of transformed cells. Several HDAC inhibitors, which contain hydrophobic tails and the Zn(2+) chelator hydroxyamic acid as a head group, are potent inhibitors of HDACs both in vitro and in vivo. In this study, a related class of compounds with a N-formyl hydroxylamino head group has been synthesized and their ability to inhibit HDACs have been assayed in biochemical and cellular assays. These compounds were found to have comparable activities to suberoylanilide hydroxyamic acid (SAHA) in HDAC enzymatic assays and histone hyperacetylation cellular assays.

MeSH terms

Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
HeLa Cells
Histone Deacetylase Inhibitors*
Histone Deacetylases / metabolism
Humans
Hydroxylamine / chemical synthesis*
Hydroxylamine / pharmacology
Jurkat Cells
U937 Cells

Substances

Enzyme Inhibitors
Histone Deacetylase Inhibitors
Hydroxylamine
Histone Deacetylases