Highly potent extranuclear-targeted luminescent iridium(iii) antitumor agents containing benzimidazole-based ligands with a handle for functionalization

Chem Commun (Camb). 2016 Dec 1;52(98):14165-14168. doi: 10.1039/c6cc07909a.

Abstract

A series of 6 substitutionally inert and luminescent iridium(iii) antitumor agents of the type [Ir(C∧N)2(N∧N)][PF6] containing a benzimidazole N∧N ligand with an ester group as a handle for further functionalization has been prepared. They exhibit IC50 values in the high nanomolar range in some ovarian and breast cancer cell lines (approximately 100× more cytotoxic than cisplatin (CDDP) in MDA-MB-231) and are located in the actin cortex predominantly as shown by confocal luminescence microscopy. This discovery could open the door to a new large family of drug bioconjugates with diverse and simultaneous functions.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Iridium / chemistry
  • Iridium / pharmacology*
  • Ligands
  • Luminescence*
  • Microscopy, Confocal
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Ligands
  • Organometallic Compounds
  • Iridium
  • benzimidazole