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

Abstract

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

Dibromo- and Dichlorotriphenylphosphino N-Acyclic Carbene Complexes of Platinum(II)—Synthesis and Cytotoxicity

“…These data prompted us to investigate solely the chlorocomplexes for the cytotoxicity on human cell lines. It has to be underlined that, while the stability in DMSO and/or water is commonly described in works dealing with the biological activity of halometal complexes [48,49,55], the stability in the presence of chloride ions is not frequently discussed [56,57]. Since in physiological conditions as well as in vitro cell assays a high concentration of chloride ions cannot be avoided, our results suggest always testing the halocomplexes' stability towards chloride ions before studying their biological properties.…”

Development of Cytotoxic GW7604-Zeise’s Salt Conjugates as Multitarget Compounds with Selectivity for Estrogen Receptor- Positive Tumor Cells

“…A modified procedure was applied to determine the influence of full cell culture medium on metal complexes. 70 To 11 mL of complete DMEM medium including 10% FCS, 11 μL of a freshly prepared 3 mM DMF solution of GW7604-Pent-PtCl 3 was added. The solution was then incubated for 4 h at 37 °C in the dark.…”

Benzimidazole-Based NHC Metal Complexes as Anticancer Drug Candidates: Gold(I) vs. Platinum(II)

“…Complexes of the type [Au(NHC)X] (X = Cl, Br, I) are readily transformed in aqueous media to cationic [Au(NHC) 2 ] + species due to an effect called ligand scrambling [39,[43][44][45]. This type of compounds showed remarkably high cytotoxic effects in numerous cancer cell lines and a higher cellular accumulation, and thus may contribute to the activity of [Au(NHC)X] complexes as their more active metabolites.…”