Synthesis and biological activity of novel deoxycholic acid derivatives

Bioorg Med Chem. 2015 Aug 1;23(15):5022-5034. doi: 10.1016/j.bmc.2015.05.012. Epub 2015 May 13.

Abstract

We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth.

Keywords: Bile acids; Biological activity; Cytotoxicity; Deoxycholic acid derivatives; Nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Deoxycholic Acid / analogs & derivatives*
  • Deoxycholic Acid / chemical synthesis
  • Deoxycholic Acid / toxicity
  • Humans
  • Isoxazoles / chemistry
  • Lipopolysaccharides / toxicity
  • Mice
  • Microwaves
  • Nitric Oxide / metabolism
  • Structure-Activity Relationship

Substances

  • Isoxazoles
  • Lipopolysaccharides
  • Deoxycholic Acid
  • Nitric Oxide