Challenge of human cells with auranofin, 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranosato-S-triethylphosphine gold(I) (Ridaura), a gold-containing compound approved by the FDA for the treatment of rheumatoid arthritis, induces the specific synthesis of a 32-kD stress protein (p32) [Caltabiano et al., Biochem. biophys. Res. Commun. 138, 1074 (1986)]. To establish a structure-activity relationship for this effect, a series of auranofin ligands, gold analogs, and other anti-arthritic agents were examined for their abilities to stimulate p32 synthesis. The results indicate that the gold atom is necessary for enhanced expression of p32. However, the structure of co-ordinated ligands also affected potency, and gold complexes bearing several phosphine or thiosugar groups exhibited the greatest activity. These data indicate that the distinct potencies of auranofin analogs probably reflect their membrane permeability and subsequent delivery of pharmacologically active concentrations of gold to the cytoplasmic compartment.
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