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