Structural basis for DNA-cleaving activity of resveratrol in the presence of Cu(II)

Bioorg Med Chem. 2006 Mar 1;14(5):1437-43. doi: 10.1016/j.bmc.2005.09.070. Epub 2005 Oct 24.


Resveratrol (1, 3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in grapes and other food products, is known as an antioxidant and cancer chemopreventive agent. However, 1 was shown to induce genotoxicity through a high frequency of micronucleus and sister chromatid exchange in vitro and DNA-cleaving activity in the presence of Cu(II). The present study was designed to explore the structure-activity relationship of 1 in DNA strand scission and to characterize the substrate specificity for Cu(II) and DNA binding. When pBR322DNA was incubated with 1 or its analogues differing in the number and positions of hydroxyl groups in the presence of Cu(II), the ability of 4-hydroxystilbene analogues to induce DNA strand scission is much stronger than that of 3-hydroxy analogues. The high binding affinity with both Cu(II) and DNA was also observed by 4-hydroxystilbene analogues. The reduction of Cu(II) which is essential for activation of molecular oxygen proceeded by addition of 1 to the solution of the Cu(II)-DNA complex, while such reduction was not observed with the addition of isoresveratrol, in which the 4-hydroxy group of 1 is changed to the 3-position. The results show that the 4-hydroxystilbene structure of 1 is a major determinant of generation of reactive oxygen species that was responsible for DNA strand scission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antioxidants / pharmacology
  • Binding Sites
  • Cations, Divalent
  • Copper / metabolism*
  • DNA / metabolism*
  • DNA Damage*
  • Hydroxyl Radical / metabolism
  • Reactive Oxygen Species
  • Resveratrol
  • Stilbenes / metabolism*
  • Structure-Activity Relationship


  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Cations, Divalent
  • Reactive Oxygen Species
  • Stilbenes
  • Hydroxyl Radical
  • 4-hydroxystilbene
  • Copper
  • DNA
  • Resveratrol