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.
J Med Chem
; 66(12): 8238-8250, 2023 06 22.
Article
en En
| MEDLINE
| ID: mdl-37294951
ABSTRACT
The reactivities of halido[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I) (chlorido (5), bromido (6), iodido (7)), bis[1,3-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.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias
/
Antineoplásicos
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Austria