Anticancer activity and DNA-binding investigations of the Cu(II) and Ni(II) complexes with coumarin derivative

Chem Biol Drug Des. 2015 Mar;85(3):385-93. doi: 10.1111/cbdd.12418. Epub 2014 Sep 15.

Abstract

Two new copper(II) (2) and nickel(II) (3) complexes with a new coumarin derivative have been synthesized and structurally characterized. The DNA-binding activities of the two complexes have been investigated by spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis, and viscosity measurements. The results indicate that the two complexes, especially the complex 2, can strongly bind to calf-thymus DNA (CT--DNA). The intrinsic binding constants Kb of the complexes with CT-DNA are 2.99 × 10(5) and 0.61 × 10(5) for 2 and 3, respectively. Comparative cytotoxic activities of the two complexes are also determined by MTT assay. The results show that the drugs designed here have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60), and human prostate (PC3) cell lines. Cell apoptosis was detected by Annexin V/PI flow cytometry, and the results show that the two copper complexes can induce apoptosis of the three human tumor cells. In conclusions, the two complexes show considerable cytotoxic activity against the three human cancer and induce apoptosis of the threes.

Keywords: DNA-binding properties; anticancer activity; cell apoptosis; coumarin derivative; human tumor cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cattle
  • Cell Line, Tumor
  • Circular Dichroism
  • Coordination Complexes / chemistry*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Copper / chemistry*
  • Coumarins / chemistry*
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Cleavage / drug effects
  • HL-60 Cells
  • Hep G2 Cells
  • Humans
  • Nickel / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Coumarins
  • Copper
  • Nickel
  • DNA
  • calf thymus DNA
  • coumarin