title: Amides of gold(I) diphosphines prepared from N-heterocyclic sources and their in vitro and in vivo screening for anticancer activity.
abstract: A series of new neutral mononuclear or dinuclear gold(I) complexes and a cyclic cationic tetranuclear amidogold(I) complex comprising of the phosphines 1,2-bis(dimethylphosphino)ethane (dmpe), μ-1,2-bis(diphenylphosphino)ethane (dppe), μ-1,3-bis(diphenylphosphino)propane (dppp), μ-1,5-bis(diphenylphosphino)pentane (dpppe), μ-1,6-bis(diphenylphosphino)hexane (dpph) or trimethylphosphine, and several N-heterocyclic ring systems (imidazolate, pyrazolate, 1,2,3-triazolate, 1,2,4-triazolate, pyrrolate, 9H-purine-9-ate or 9H-purine-6-amine-9-ate) as ligands, reveal intermolecular aurophilic interactions and 2D channels available for solvent molecules in some of their crystal structures. The antitumour activity of the acyclic gold(I) compounds is highly dependent on the substituents on the phosphorus atoms being highest for phenyl groups and lower for methyl groups. The activity of these compounds against selected cell lines is linked to the length of the carbon bridge between the two phosphorus atoms being highest with a bridge consisting of 5 or 6 carbons. Two compounds with the highest tumour specifities that contain dpppe and pyrazolate (a lipophilic compound) or 1,2,4-triazolate (a hydrophilic compound) induce an apoptotic cell death pathway and a maximum dose to Balb/C mice is tolerated.
authors.affiliation: Department of Chemistry and Polymer Science, University of Stellenbosch, Matieland, Stellenbosch, South Africa.
authors.forename: Ulrike E I
authors.initials: UE
authors.lastname: Horvath
authors.forename: Liliana
authors.initials: L
authors.lastname: Dobrzańska
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Strasser
authors.forename: Wilna
authors.initials: W
authors.lastname: Bouwer Neé Potgieter
authors.forename: Gisela
authors.initials: G
authors.lastname: Joone
authors.forename: Constance E Jansen
authors.initials: CE
authors.lastname: van Rensburg
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cronje
authors.forename: Helgard G
authors.initials: HG
authors.lastname: Raubenheimer
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D010720:Phosphines / Q000737:chemistry*; D018675:Toxicity Tests; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D050607:Organogold Compounds; D010720:Phosphines; D006046:Gold