Reaction Behavior of [1,3-Diethyl-4,5-diphenyl-1 H -imidazol-2-ylidene] Containing Gold(I/III) Complexes against Ingredients of the Cell Culture Medium and the Meaning on the Potential Use for Cancer Eradication Therapy.

The reactivities of halido[1,3-diethyl-4,5-diphenyl-1 H -imidazol-2-ylidene]gold(I) (chlorido ( 5 ), bromido ( 6 ), iodido ( 7 )), bis[1,3-diethyl-4,5-diphenyl-1 H -imidazol-2-ylidene]gold(I) ( 8 ), and bis[1,3-diethyl-4,5-diphenyl-1 H -imidazol-2-ylidene]dihalidogold(III) (chlorido ( 9 ), bromido ( 10 ), iodido ( 11 )) complexes against ingredients of the cell culture medium were analyzed by HPLC. The degradation in the RPMI 1640 medium was studied, too. Complex 6 quantitatively reacted with chloride to 5 , while 7 showed additionally ligand scrambling to 8 . Interactions with non-thiol containing amino acids could not be detected. However, glutathione (GSH) reacted immediately with 5 and 6 yielding the (NHC)gold(I)-GSH complex 12 . The most active complex 8 was stable under in vitro conditions and strongly participated on the biological effects of 7 . The gold(III) species 9 - 11 were completely reduced by GSH to 8 and are prodrugs. All complexes were tested for inhibitory effects in Cisplatin-resistant cells, as well as against cancer stem cell-enriched cell lines and showed excellent activity. Such compounds are of utmost interest for the therapy of drug-resistant tumors.