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

Abstract

A series of four tetraalkylammonium gold(III) salts, [R 4N] +[AuX 4] − (R  Et, Bu; X  Cl,Br) and five tetraalkylammonium gold(I) salts, [R 4N] +- [AuX 2] − [R  Et, Bu; X  Cl, Br, C 6H 5S, S-Glucose- (OAc) 4] were prepared, together with [(Et 3P) 2Au +]- [AuCl 2] − ( 16) and evaluated for their oral antiinflammatory [Au(III)] and antiarthritic activity [Au(I)] in comparison with the gold compounds auranofin [Et 3PAuS-Glucose(OAc) 4] (AF) and [(Et 3P) 2Au] +- Cl −( 4). Synthesis of the complexes [R 4N] +[AuX 2] − (R  Et, Bu; X  Cl, Br) was accomplished by reduction of the corresponding Au(IlI) complex with C 6H 5NHNH 2 (X  Cl) or acetone (X  Br). RS −displacement of Br − from [(Bu) 4N] +[AuBr 2] − gave the thiolates [(Bu 4)N] +[Au(SR) 2] − [R  C 6H 5; 2, 3, 4, 6- Glucose(OAc) 4]. Admixture in EtOH of [(Et 3P) 2Au] +Cl with HAuCl 4 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 0.6 μg/ ml suggesting poor oral bioavailability. In contrast [(Et 3P) 2Au +] [AuCl 2] − ( 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.