Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction

Eur J Med Chem. 2018 Aug 5;156:148-161. doi: 10.1016/j.ejmech.2018.06.056. Epub 2018 Jun 25.


Fluorescent 4-ethylthio-1,8-naphthalimides containing rhodium(I) N-heterocyclic carbene (NHC) and ruthenium (II) NHC fragments were synthesised and evaluated for their antiproliferative effects, cellular uptake and DNA-binding activity. Both types of organometallics triggered ligand dependent efficient cytotoxic effects against tumor cells with the rhodium(I) NHC derivatives causing stronger effects than the ruthenium (II) NHC analogues. Antiproliferative effects could also be observed against several pathogenic Gram-positive bacterial strains, whereas the growth of Gram-negative bacteria was not substantially affected. Cellular uptake was confirmed by atomic absorption spectroscopy as well as by fluorescence microscopy indicating a general ligand dependent accumulation in the cells. An in-depth study on the interaction with DNA confirmed insertion of the naphthalimide moiety between the planar bases of B-DNA via an intercalation mechanism, as well as its stacking on top of the quartets of G-quadruplex structures. Furthermore, additional coordinative binding of the organometallic complexes to the model DNA base 9-ethylguanine could be detected. The studied compounds thus represent promising bioorganometallics featuring strong pharmacological effects in combination with excellent cellular imaging properties.

Keywords: Bioorganometallics; Carbene; Naphthalimide; Rhodium; Ruthenium.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacology
  • G-Quadruplexes / drug effects
  • Humans
  • Intercalating Agents / chemistry*
  • Intercalating Agents / pharmacology
  • Ligands
  • Naphthalimides / chemistry*
  • Naphthalimides / pharmacology
  • Neoplasms / drug therapy
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Rhodium / chemistry*
  • Rhodium / pharmacology
  • Ruthenium / chemistry*
  • Ruthenium / pharmacology


  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Intercalating Agents
  • Ligands
  • Naphthalimides
  • Organometallic Compounds
  • Ruthenium
  • Rhodium