title: Heteroditopic P,N ligands in gold(I) complexes: synthesis, structure and cytotoxicity.
abstract: New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT=tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp(3)-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I). These findings were supported by results from the 60-cell line fingerprint screen of the Developmental Therapeutics Programme of the National Institutes of Health for two promising compounds. The cytotoxicity of some of these ligands and gold(I)complexes is due to the induction of apoptosis. The ligands and gold(I)complexes demonstrated selective toxicity towards specific cell lines, with Jurkat T cells being more sensitive to the cytotoxic effects of these compounds, while the non-cancerous human cell line KMST6 proved more resistant when compared to the cancerous cell lines. Results from the NIH DTP 60 cell-line fingerprint screen support the observed enhancement of cytotoxicity upon gold(I) complexation. One gold(I)complex induced high levels of apoptosis at concentrations of 50 μM in all the cell lines screened in this study, while some of the other compounds selectively induced apoptosis in the cell lines. These results point towards the potential for selective toxicity to cancerous cells through the induction of apoptosis.
authors: Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa; Advanced Materials Division, Mintek, 200 Malibongwe Drive, Strijdom Park 2125, South Africa.
authors: Telisha
authors: T
authors: Traut-Johnstone
authors: Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
authors: Stonard
authors: S
authors: Kanyanda
authors: Advanced Materials Division, Mintek, 200 Malibongwe Drive, Strijdom Park 2125, South Africa.
authors: Frederik H
authors: FH
authors: Kriel
authors: Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
authors: Tanya
authors: T
authors: Viljoen
authors: Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
authors: P D Riekert
authors: PD
authors: Kotze
authors: Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa; School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban, 4000, South Africa.
authors: Werner E
authors: WE
authors: van Zyl
authors: Advanced Materials Division, Mintek, 200 Malibongwe Drive, Strijdom Park 2125, South Africa.
authors: Judy
authors: J
authors: Coates
authors: Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
authors: D Jasper G
authors: DJ
authors: Rees
authors: Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
authors: Mervin
authors: M
authors: Meyer
authors: Advanced Materials Division, Mintek, 200 Malibongwe Drive, Strijdom Park 2125, South Africa.
authors: Raymond
authors: R
authors: Hewer
authors: Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa; Ferrier Research Institute, Victoria University of Wellington, 69 Gracefield Rd, Lower Hutt 5010, New Zealand. Electronic address: bwilliams@uj.ac.za.
authors: D Bradley G
authors: DB
authors: Williams
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D010758:Phosphorus / Q000737:chemistry*
chemical_list: D008024:Ligands; D010758:Phosphorus; D006046:Gold; D009584:Nitrogen
keywords: Cytotoxicity; Gold(I) complexes; Metal-based drugs; P,N ligands