Gold(I) N-heterocyclic carbene complexes show strong proapoptotic, antioxidant and anti-inflammatory effects in A2780 and endothelial cells

• DOI: 10.1016/j.cbi.2025.111381
• Publication Date: 2025-01-16T07:44:23Z
• Authors: Zdeněk Trávníček; Ján Vančo; Michal Čajan; Tomáš Malina; Zdeněk Dvořák; René Lenobel; Barbora Beláková; Johannes A. Schmid
• Keywords: Anti-inflammatory

A series of eight gold(I) N-heterocyclic carbene (NHC) complexes [Au(IMes)(Ln)] based on 1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene (IMes) and 7-azaindole derivatives (HLn), where n = 1-8 for HL1 = 5-fluoro7-azaindole, HL2 = 5-bromo-7-azaindole, HL3 = 3-chloro-7-azaindole, HL4 = 3-iodo-7-azaindole, HL5 = 5bromo-3-chloro-7-azaindole, HL6 = 5-bromo-3-iodo-7-azaindole, HL7 = 4-chloro-2-methyl-7-azaindole and HL8 = 7-azaindole, was prepared, characterised and studied for their in vitro anti-cancer and anti-inflammatory effects. The complexes showed significant cytotoxicity on human ovarian cancer cell lines (A2780, IC50 approximate to 8-19 mu M and A2780R, IC50 approximate to 8-19 mu M) and lowered toxicity in normal HaCat and MRC-5 cells. Cellular effects of the selected complexes 1 and 7 were evaluated in A2780 cells using flow cytometry. Moreover, the time-dependent cellular uptake in A2780 cells, a shotgun proteomic analysis, an ESI-MS study of hydrolysis and interactions with L-cysteine and reduced glutathione (GSH) were performed. Complexes 1 and 7 revealed remarkable antiinflammatory effects via inhibition of NF-kappa B activity in human endothelial cells.