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

The reactivitiesof 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)) complexesagainst 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 couldnot 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 biologicaleffects of 7. The gold(III) species 9-11 were completely reduced by GSH to 8 and areprodrugs. All complexes were tested for inhibitory effects in Cisplatin-resistantcells, as well as against cancer stem cell-enriched cell lines andshowed excellent activity. Such compounds are of utmost interest forthe therapy of drug-resistant tumors.

Automated summary

The reactivities of gold complexes with different ligands were analyzed in cell culture medium. Complexes 6 and 7 showed significant reactions, while interactions with non-thiol containing amino acids were not detected. Complex 8 exhibited strong stability and contributed to the biological effects of complex 7. The gold(III) species were reduced by GSH and showed promising activity against drug-resistant tumors.