title: A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer.
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. 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.
authors.affiliation: 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.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Hockey
authors.affiliation: Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Barbante
authors.affiliation: Strategic Research Center for Chemistry and Biotechnology, Deakin University, Pigdons Road, Waurn Ponds, 3216, Victoria, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Francis
authors.affiliation: 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.
authors.forename: Jarrad M
authors.initials: JM
authors.lastname: Altimari
authors.affiliation: Metabolic Genetic Disease Laboratory, Deakin School of Medicine, Locked Bag 20000, Geelong Victoria, 3220, Australia.
authors.forename: Prusothman
authors.initials: P
authors.lastname: Yoganantharajah
authors.affiliation: Metabolic Genetic Disease Laboratory, Deakin School of Medicine, Locked Bag 20000, Geelong Victoria, 3220, Australia.
authors.forename: Yann
authors.initials: Y
authors.lastname: Gibert
authors.affiliation: 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. Electronic address: luke.henderson@deakin.edu.au.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Henderson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D057930:Click Chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007495:Iridium / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D014230:Triazoles; D007495:Iridium; D053148:Caspase 3
keywords: Click chemistry; Iridium; Prostate cancer; Triazole