Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes

J Inorg Biochem. 2011 Feb;105(2):119-26. doi: 10.1016/j.jinorgbio.2010.11.008. Epub 2010 Nov 16.

Abstract

Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] (1) and [Cu(acac)(dppz)Cl] (2) (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) >1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC(50) values of 5.25±0.83 μM (1) and 4.40±0.52 μM (2) in the natural light, and 2.57±0.92 μM (1) and 2.18±0.52 μM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cattle
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper*
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA Cleavage / drug effects*
  • DNA Cleavage / radiation effects
  • Drug Design
  • Drug Evaluation, Preclinical
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Light
  • Molecular Conformation
  • Structure-Activity Relationship
  • Ultraviolet Rays

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Copper
  • DNA
  • calf thymus DNA