9-Octadecynoic Acid: A Novel DNA Binding Agent

Chem Res Toxicol. Mar-Apr 1991;4(2):195-8. doi: 10.1021/tx00020a011.

Abstract

A novel bioassay was developed to permit the identification of cytotoxic natural principles that bind to DNA. A hexane extract of Schoepfia californica cytotoxic to cultured KB cells displayed much less cytotoxic potential when the culture medium contained exogenously added calf thymus DNA. Fractionation of the extract afforded a purified principle shown to be 9-octadecynoic acid, an 18-carbon, unbranched acetylenic fatty acid. 9-Octadecynoic acid had an apparent DNA dissociation constant of 1.8 mM; it inhibited topoisomerase I mediated DNA filter binding but did not inhibit the DNA topoisomerase I mediated relaxation of a supercoiled plasmid DNA. The fatty acid was weakly inhibitory to DNA polymerase alpha. 9-Octadecynoic acid possesses none of the structural characteristics of known DNA binding molecules and may bind to DNA by some novel mechanism.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alkynes
  • Animals
  • Cells, Cultured
  • DNA / metabolism*
  • DNA Polymerase II / metabolism
  • DNA Topoisomerases, Type I / drug effects
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Fatty Acids, Unsaturated / metabolism*
  • Humans
  • KB Cells / cytology
  • KB Cells / drug effects

Substances

  • Alkynes
  • Fatty Acids, Unsaturated
  • 9-stearolic acid
  • Doxorubicin
  • Adenosine Triphosphate
  • DNA
  • DNA Polymerase II
  • DNA Topoisomerases, Type I