Gold I Complexes with Monodentate Phosphines

The nature of the phosphine ligand (R3P) influenced the extent of oral absorption of the complex and antiarthritic activity was found to be closely related to the gold serum concentrations (Fig. 3). The maximum absorption and activity occurred when the phosphine was EtsP. EtaPAuCl was initially selected for clinical trial but diarrhoea proved to be a troublesome side-effect and it was abandoned in favour of the tetraacetylated thioglucose derivative, auranofin (9). Under the tradename Ridaura this was approved by the FDA for clinical use in the USA in May 1985. 

The results of clinical trials on auranofin to date suggest that its efficacy approaches that of gold(I)thiomalate and it is relatively well tolerated in most patients. Auranofin appears to have a contrasting pharmokinetic profile to aurothiomalate (Table 3). The higher percentages of oral absorption, cell-associated gold and faecal compared to renal excretion, can all be attributed to the high lipophilidty of the complex. 

2 Cytotoxicity and Antitumour Activity ofAu(I) Phosphine Complexes 

Lorber and coworkers demonstrated that auranofin exhibited antiproliferative effects against cultured human cancer cells They also reported that auranofin increased the survival times of mice with P388 leukaemia A number of Au(I) complexes of PhsP have also been reported to have anticancer activity  

The antitumour activity and cytotoxicity of a large number of gold(I) complexes have also been evaluated Au(I) thiolate complexes exhibit very low cytotoxicity to cancer 

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Linear Gold(I) Complexes with Monodentate Phosphine, Arsine or Stibine Ligands 882... 

The most commonly observed gold(I) compound is a linear two-coordinate complex. Three- and four-coordinate complexes, which wiU be discussed here and in the foUowing section, are substantially less common. Several examples " of three-coordinate complexes are known, some with monodentate phosphine and some with bidentate phosphine ligands. The observation that these complexes have significant antitumor activity has increased interest in these species . The purpose of this work is to calculate the structures of complexes with Au+ bonded to three neutral ligands in order to compare it to the other types of gold(l) complexes discussed above. 

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