Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction

Eur J Med Chem. 2013:70:640-8. doi: 10.1016/j.ejmech.2013.10.031. Epub 2013 Oct 22.

Abstract

Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC₅₀ values ranging from 0.31 to 30.76 μM. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA.

Keywords: Copper(II) complexes; Crystal structure; Cytotoxicity; Isoquinoline; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Copper / chemistry*
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / drug effects*
  • Dioxoles / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Isoquinolines / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • 5-pyridin-2-yl-(1,3)dioxolo(4,5-g)isoquinoline
  • Antineoplastic Agents
  • DNA, Neoplasm
  • Dioxoles
  • Isoquinolines
  • Organometallic Compounds
  • Copper