Unusual DNA binding modes for metal anticancer complexes

Biochimie. 2009 Oct;91(10):1198-211. doi: 10.1016/j.biochi.2009.03.017. Epub 2009 Apr 1.

Abstract

DNA is believed to be the primary target for many metal-based drugs. For example, platinum-based anticancer drugs can form specific lesions on DNA that induce apoptosis. New platinum drugs can be designed that have novel modes of interaction with DNA, such as the trinuclear platinum complex BBR3464. Also it is possible to design inert platinum(IV) pro-drugs which are non-toxic in the dark, but lethal when irradiated with certain wavelengths of light. This gives rise to novel DNA lesions which are not as readily repaired as those induced by cisplatin, and provides the basis for a new type of photoactivated chemotherapy. Finally, newly emerging ruthenium(II) organometallic complexes not only bind to DNA coordinatively, but also by H-bonding and hydrophobic interactions triggered by the introduction of extended arene rings into their versatile structures. Intriguingly osmium (the heavier congener of ruthenium) reacts differently with DNA but can also give rise to highly cytotoxic organometallic complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / chemistry
  • Cisplatin / therapeutic use
  • DNA / chemistry
  • DNA / drug effects*
  • Humans
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / therapeutic use
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / therapeutic use
  • Photochemistry / methods
  • Prodrugs / chemistry
  • Prodrugs / therapeutic use

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Organoplatinum Compounds
  • Prodrugs
  • DNA
  • Cisplatin