6,6″-Dimethyl-2,2':6',2″-terpyridine revisited: new fluorescent silver(I) helicates with in vitro antiproliferative activity via selective nucleoli targeting

Eur J Med Chem. 2014 Oct 30:86:456-68. doi: 10.1016/j.ejmech.2014.09.004. Epub 2014 Sep 4.

Abstract

6,6″-Dimethyl-2,2':6',2″-terpyridine ligand (L) reacts in equimolar ratio with Ag(I) ions what results in formation of dinuclear double helicates, which differ in terms of framework and complexity in accordance to counterions and solvent applied. Obtained complexes were thoroughly studied in terms of their biological activity, with the positive antiproliferative outcome on three human cancer cell lines: human breast cancer (T47D), human cervical carcinoma (HeLa) and human lung cancer (A-549). Performed DNA binding experiments showed that given Ag(I) species specifically interact with DNA double helix via intercalation and were visualized by confocal microscopy to specifically bind to the nuclei. All newly synthesized helical systems exhibit promising antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains. Spectrophotometric properties were described as fulfilment of structural studies of newly presented complexes confirming their helical structure in solution.

Keywords: Antibacterial activity; Confocal microscopy; Cytotoxicity; Silver(I) helical complex; Spectroscopic DNA binding experiments; Terpyridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleolus / drug effects*
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Escherichia coli / drug effects*
  • Fluorescence
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Silver / chemistry*
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship

Substances

  • 6,6''-dimethyl-2,2':6',2''-terpyridine
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Organometallic Compounds
  • Pyridines
  • Silver