A mechanistic study on the nuclease activities of some hydroxystilbenes

Bioorg Med Chem. 2004 Mar 1;12(5):1231-7. doi: 10.1016/j.bmc.2003.10.062.

Abstract

The nuclease activities of a series of hydroxystilbeneoids have been studied so as to establish a structure-activity correlation and deduce the mechanistic pathway of the process. Although the test compounds could nick plasmid DNA, only three of these including resveratrol produced double strand breaks in DNA. Amongst these new stilbenes, compound 2e containing a partially methylated catechol and a C-4 hydroxy moieties was equally potent as resveratrol. The activities of the unprotected catechol-derivatives were less than those of the resorcinol-derivatives, which were, however, compensated by partial methylation of the former. The presence of Cu(2+) and O(2) and the participation of a Cu(+)-oxo intermediate were obligatory in the process which did not require addition of any external reducing agent. Overall, the differential nuclease activities of the compounds could be explained primarily with their superoxide anion generation abilities, and to a lesser extent with their DNA binding and Cu(2+) reducing capacities. The amount of superoxide anion produced by the compounds depended strongly on their Cu(+)-complexation abilities, which again, was decided by the pattern and nature of the oxygenated substituents in the aromatic rings.

MeSH terms

  • Catechols
  • Copper
  • DNA / metabolism*
  • DNA Damage / drug effects
  • Deoxyribonucleases
  • Oxidation-Reduction
  • Oxygen
  • Plasmids / metabolism*
  • Resorcinols
  • Resveratrol
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship
  • Superoxides / metabolism

Substances

  • Catechols
  • Resorcinols
  • Stilbenes
  • Superoxides
  • Copper
  • DNA
  • Deoxyribonucleases
  • catechol
  • Resveratrol
  • Oxygen
  • resorcinol