Reaction Behavior of 1,3-Diethyl-4,5-diphenyl‑1H‑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

摘要

The reactivities of halido­[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]­gold­(I) (chlorido (5), bromido (6), iodido (7)), bis­[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]­gold­(I) (8), and bis­[1,3-diethyl-4,5-diphenyl-1H-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.