A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer

Date

2016

Authors

Hockey, S.C.
Barbante, G.J.
Francis, P.S.
Altimari, J.M.
Yoganantharajah, P.
Gibert, Y.
Henderson, L.C.

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European Journal of Medicinal Chemistry, 2016; 109:305-313

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Abstract

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. Reevaluation 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.

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Copyright 2015 Elsevier Masson SAS

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