Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells

Bioorg Med Chem. 2014 Jan 1;22(1):585-93. doi: 10.1016/j.bmc.2013.10.049. Epub 2013 Nov 7.

Abstract

Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the C-ring, displays anti-inflammatory and inhibitory activities with respect to tumor cells with a high selectivity index value.

Keywords: Biological activity; Cytotoxicity; Glycyrrhetinic acid derivatives; Nitric oxide; Selectivity index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Glycyrrhetinic Acid / analogs & derivatives
  • Glycyrrhetinic Acid / chemical synthesis*
  • Glycyrrhetinic Acid / chemistry
  • Humans
  • Lipopolysaccharides
  • Neoplasms / chemistry*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / chemistry
  • Structure-Activity Relationship

Substances

  • Lipopolysaccharides
  • Nitric Oxide
  • Glycyrrhetinic Acid