The Sulfhydryl-Shuttle Model

The hydrophilic gold(I) drugs which need to be injected such as AuSTm and AuSTg, cannot easily move into most cells. Instead, they bind to cell surfaces where they can alter membrane transport and affect the overall cell metabolism [115, 134]. 

Red cells provide a useful model for studying the likely movement of gold into and out of cells. Itwas shown that Et3PAuCl moving into red cells binds to glutathione and hemoglobin [84, 85] providing ancillary evidence for the sulfhydryl shuttle. Similarly, [Au(CN)2] has been shown to enter red cells by the sulfhydryl shuttle and its uptake can be blocked by alkylation of membrane thiols [32]. 

Excluding gold complexes that caimot transverse the membrane such as AuSTm, intracellular gold concentrations must approach equilibrium with extracellular gold concentrations if active transport is not at work. The balance of gold between the environment of a cell and within the cell will depend on the ligands available. 

Many gold compounds have been tested for their potential antitumor activity by examining their cytotoxicity against cell lines in culture. This avoids barriers that arise in vivo due to uncertain absorption, restricted distribution, and variable metabolism of drugs. 

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Figure 8 The sulfhydryl shuttle model for Et3PAu+ accumulation and efflux through cellular membranes. CSH and RSH = cellular and extracellular thiols, protein, or small molecule MSH = membrane sulfhydryl-dependent transport systems...

Figure 3 The Sulfhydryl Shuttle Model (adapted from Ref. 32). MSH = membrane...

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