"Half-sandwich" Schiff-base Ir(III) complexes as anticancer agents

Eur J Med Chem. 2017 Sep 29:138:72-82. doi: 10.1016/j.ejmech.2017.06.027. Epub 2017 Jun 15.

Abstract

A series of "half-sandwich" Schiff-base Ir(III) complexes were synthesized and investigated for their in vitro activities against the leukemia K562 cell line. These compounds demonstrated antiproliferative activities against K562 cells with IC50 values of 0.26-4.77 μM. In particular, compound 10c showed cytotoxicity against five cancer cell lines/sublines and stronger activities than cisplatin in K562, K562/A02, MCF-7, MCF-7/ADM, and A549 cells. Mechanism studies illustrated that compound 10c increased the level of reactive oxygen species and induced apoptosis of K562 cells. This compound effectively decreased the mitochondrial membrane potential and the protein level of Bcl-2. It also increased the protein levels of Bax, caspase-3, and caspase-9, and led to release of cytochrome c in K562 cells, indicating that the apoptosis induced by compound 10c was mediated by the intrinsic mitochondria apoptosis pathway.

Keywords: Antiproliferative activities; Apoptosis; Reactive oxygen species; Schiff-base Ir(III) complexes.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Iridium / chemistry
  • Iridium / pharmacology*
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Schiff Bases
  • Iridium