Evaluation of some tetraalkylammonium gold(I) and gold(III) aurate salts for oral antiinflammatory and antiarthritic activity

A series of four tetraalkylammonium gold(III) salts, [R4N]+[AuX4]− (R  Et, Bu; X  Cl,Br) and five tetraalkylammonium gold(I) salts, [R4N]+- [AuX2]− [R  Et, Bu; X  Cl, Br, C6H5S, S-Glucose- (OAc)4] were prepared, together with [(Et3P)2Au+]- [AuCl2]− (16) and evaluated for their oral antiinflammatory [Au(III)] and antiarthritic activity [Au(I)] in comparison with the gold compounds auranofin [Et3PAuS-Glucose(OAc)4] (AF) and [(Et3P)2Au]+- Cl−(4). Synthesis of the complexes [R4N]+[AuX2]− (R  Et, Bu; X  Cl, Br) was accomplished by reduction of the corresponding Au(IlI) complex with C6H5NHNH2 (X  Cl) or acetone (X  Br). RS−displacement of Br− from [(Bu)4N]+[AuBr2]− gave the thiolates [(Bu4)N]+[Au(SR)2]− [R  C6H5; 2, 3, 4, 6- Glucose(OAc)4]. Admixture in EtOH of [(Et3P)2Au]+Cl with HAuCl4 gave 16. Evaluation of the four Au(Ill) salts in the carrageenan-induced rat paw edema assay at 20 mg of Au/kg showed little antiinflammatory activity on oral administration (p.o.). The five Au(I) complexes were found to be devoid of significant antiarthritic activity in the adjuvant-induced arthritic rat emodel upon oral administration. Moreover, serum gold levels were below 0.6μg/ ml suggesting poor oral bioavailability. In contrast [(Et3P)2Au+] [AuCl2]− (16) was found to be orally effective with serum Au levels of 5.6 μg/ml and demonstrated significant antiarthritic activity comparable to both AF and the salt 4.