Total synthesis and cytotoxicity evaluation of all ochratoxin A stereoisomers

Bioorg Med Chem. 2010 Jan 1;18(1):343-7. doi: 10.1016/j.bmc.2009.10.050. Epub 2009 Oct 30.

Abstract

The mycotoxin ochratoxin A is a potent inhibitor of the protein biosynthesis and known to be cytotoxic in nanomolar concentrations. In order to investigate the relationship between stereochemistry and cytotoxicity of this compound, all four ochratoxin A stereoisomers have been synthesized. Using the liver cell line Hep G2, the compounds were tested for cytotoxic and apoptotic potential. It could be shown, that the l-configuration of the phenylalanine moiety of the molecule is mostly responsible for the high cytotoxicity of ochratoxin A while the stereocenter at the dihydroisocoumarine structure is of less importance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cytotoxins / chemical synthesis*
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology*
  • Hep G2 Cells
  • Humans
  • Molecular Structure
  • Ochratoxins / chemical synthesis*
  • Ochratoxins / chemistry
  • Ochratoxins / pharmacology*
  • Stereoisomerism

Substances

  • Cytotoxins
  • Ochratoxins
  • ochratoxin A