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.
European journal of medicinal chemistry. 2015 Dec 21 [Epub ahead of print]
Samantha C Hockey, Gregory J Barbante, Paul S Francis, Jarrad M Altimari, Prusothman Yoganantharajah, Yann Gibert, Luke C Henderson
Carbon Nexus, Institute for Frontier Materials, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia; Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia. , Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia. , Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia. , Carbon Nexus, Institute for Frontier Materials, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia; Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia. , Metabolic Genetic Disease Laboratory, Deakin School of Medicine, Locked Bag 20000, Geelong Victoria, 3220, Australia. , Metabolic Genetic Disease Laboratory, Deakin School of Medicine, Locked Bag 20000, Geelong Victoria, 3220, Australia. , Carbon Nexus, Institute for Frontier Materials, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia; Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia.