Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent

Takayoshi Suzuki; Azusa Matsuura; Akiyasu Kouketsu; Shinya Hisakawa; Hidehiko Nakagawa; Naoki Miyata

doi:10.1016/j.bmc.2005.04.002

Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent

Bioorg Med Chem. 2005 Jul 1;13(13):4332-42. doi: 10.1016/j.bmc.2005.04.002.

Authors

Takayoshi Suzuki¹, Azusa Matsuura, Akiyasu Kouketsu, Shinya Hisakawa, Hidehiko Nakagawa, Naoki Miyata

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp

PMID: 15927839
DOI: 10.1016/j.bmc.2005.04.002

Abstract

A series of suberoylanilide hydroxamic acid (SAHA)-based non-hydroxamates was designed, synthesized, and evaluated for their histone deacetylase (HDAC) inhibitory activity. Among these, methyl sulfoxide 15 inhibited HDACs in enzyme assays and caused hyperacetylation of histone H4 while not inducing the accumulation of acetylated alpha-tubulin in HCT116 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation / drug effects*
Cell Proliferation / drug effects
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
HCT116 Cells
Histone Deacetylase Inhibitors*
Histone Deacetylases / chemistry
Histone Deacetylases / metabolism*
Histones / metabolism
Humans
Hydroxamic Acids / chemical synthesis*
Hydroxamic Acids / chemistry
Hydroxamic Acids / pharmacology
Structure-Activity Relationship
Tubulin Modulators
Vorinostat

Substances

Enzyme Inhibitors
Histone Deacetylase Inhibitors
Histones
Hydroxamic Acids
Tubulin Modulators
Vorinostat
Histone Deacetylases