ZFIN ID: ZDB-PUB-160124-3
A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer
Hockey, S.C., Barbante, G.J., Francis, P.S., Altimari, J.M., Yoganantharajah, P., Gibert, Y., Henderson, L.C.
Date: 2016
Source: European Journal of Medicinal Chemistry   109: 305-313 (Journal)
Registered Authors: Gibert, Yann
Keywords: Click chemistry, Iridium, Prostate cancer, Triazole
MeSH Terms:
  • Animals
  • Antineoplastic Agents/chemical synthesis
  • Antineoplastic Agents/chemistry*
  • Antineoplastic Agents/pharmacology*
  • Apoptosis/drug effects
  • Caspase 3/metabolism
  • Cell Line, Tumor
  • Click Chemistry
  • Coordination Complexes/chemical synthesis
  • Coordination Complexes/chemistry*
  • Coordination Complexes/pharmacology*
  • Humans
  • Iridium/chemistry*
  • Iridium/pharmacology*
  • Ligands
  • Male
  • Prostate/drug effects
  • Prostate/metabolism
  • Prostate/pathology
  • Prostatic Neoplasms/drug therapy*
  • Prostatic Neoplasms/metabolism
  • Prostatic Neoplasms/pathology
  • Triazoles/chemical synthesis
  • Triazoles/chemistry
  • Triazoles/pharmacology
  • Zebrafish
PubMed: 26802546 Full text @ Eur. J. Med. Chem.
A range of 1,4-substituted 2-pyridyl-N-phenyl triazoles were synthesised and evaluated for their antiproliferative properties against lymph node cancer of the prostate (LNCaP) and bone metastasis of prostate cancer (PC-3) cells. Excellent-to-low IC50 values were determined (5.6-250 μM), and a representative group of 4 ligands were then complexed to iridium(III) giving highly luminescent species. Re-evaluation of these compounds against both cell lines was then undertaken and improved potency (up to 72-fold) was observed, giving IC50 values of 0.36-11 μM for LNCaP and 0.85-5.9 μM for PC-3. Preliminary screens for in vivo toxicity were conducted using a zebrafish model showing a wide range of induced toxicity depending of the compound evaluated. Apoptosis and Caspase-3 levels were also determined and showed no statistical difference between some of the treated specimens and the controls. This study may identify novel therapeutic agents for advanced stage of prostate cancer in humans.