Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid

J Med Chem. 2008 Aug 14;51(15):4834-8. doi: 10.1021/jm800167u. Epub 2008 Jul 4.

Abstract

Novel furoxan-based nitric oxide (NO) releasing derivatives of oleanolic acid (OA) were synthesized for potential therapy of liver cancers. Six compounds produced high levels of NO in human hepatocellular carcinoma (HCC) cells and exhibited strong cytotoxicity selectively against HCC in vitro. Treatment with 8b or 16b significantly inhibited the growth of HCC tumors in vivo. These data provide a proof-in-principle that furoxan/OA hybrids may be used for therapeutic intervention of human liver cancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Drug Design
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Oleanolic Acid / chemical synthesis*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Nitric Oxide
  • Oleanolic Acid