Structure-activity relationship studies of a series of novel delta-lactam-based histone deacetylase inhibitors

J Med Chem. 2007 May 31;50(11):2737-41. doi: 10.1021/jm0613828. Epub 2007 May 4.

Abstract

We synthesized a series of delta-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated anti-inflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-alpha and nitric oxide by LPS-stimulated RAW264.7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors*
  • Humans
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lactams / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Models, Molecular
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Structure-Activity Relationship
  • Transplantation, Heterologous
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Lactams
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide