Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors

Satoshi Osada; Satoshi Sano; Mariko Ueyama; Yoshiro Chuman; Hiroaki Kodama; Kazuyasu Sakaguchi

doi:10.1016/j.bmc.2009.12.005

Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors

Bioorg Med Chem. 2010 Jan 15;18(2):605-11. doi: 10.1016/j.bmc.2009.12.005. Epub 2009 Dec 28.

Authors

Satoshi Osada¹, Satoshi Sano, Mariko Ueyama, Yoshiro Chuman, Hiroaki Kodama, Kazuyasu Sakaguchi

Affiliation

¹ Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, 1 Honjo, Saga 840-8502, Japan. osadas@cc.saga-u.ac.jp

PMID: 20036560
DOI: 10.1016/j.bmc.2009.12.005

Abstract

Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds.

Publication types

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

MeSH terms

Drug Design
HeLa Cells
Histone Deacetylase Inhibitors / chemical synthesis
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydrocarbons, Fluorinated / chemistry*
Molecular Structure
Stereoisomerism
Structure-Activity Relationship
Thioacetamide / analogs & derivatives
Thioacetamide / chemistry
Thioacetamide / pharmacology*

Substances

Histone Deacetylase Inhibitors
Hydrocarbons, Fluorinated
Thioacetamide