2. Academic Validation
  3. Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors

Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors

  • J Med Chem. 2002 Jun 20;45(13):2877-85. doi: 10.1021/jm020154k.
Soon Hyung Woo 1,  Sylvie Frechette,  Elie Abou Khalil,  Giliane Bouchain,  Arkadii Vaisburg,  Naomy Bernstein,  Oscar Moradei,  Silvana Leit,  Martin Allan,  Marielle Fournel,  Marie-Claude Trachy-Bourget,  Zuomei Li,  Jeffrey M Besterman,  Daniel Delorme
Affiliations

Affiliation

  • 1 Departments of Medicinal Chemistry and Molecular Biology, MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.
PMID: 12061890 DOI: 10.1021/jm020154k
Abstract

A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar IC(50) values, comparable to natural TSA. These compounds induce hyperacetylation of histones in T24 human Cancer cells and significantly inhibit proliferation in various human Cancer cells. They also induce expression of p21 and cause cell cycle blocks in human Cancer cells. In this paper, we describe the synthesis of these new compounds as well as structure-activity relationship results from Enzyme inhibition and alterations in cellular function.

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