Mixed valence copper(I,II) binuclear complexes with unexpected structure: synthesis, biological properties and anticancer activity

J Med Chem. 2014 Jul 24;57(14):6252-8. doi: 10.1021/jm500154f. Epub 2014 Jul 8.

Abstract

We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Copper / chemistry*
  • Crystallography, X-Ray
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Copper