Gold(I) N‑Heterocyclic
Carbene Complexes with
7‑Azaindoles Demonstrates In Vitro Antiproliferative Effects
on Ovarian Cancer Cells and Anti-inflammatory Activity
posted on 2024-05-07, 14:04authored byJan Belza, Zdeněk Trávníček, Ján Vančo, Michal Čajan, Jan Hošek, Zdeněk Dvořák
The gold(I) N-heterocyclic carbene (NHC) complexes, containing
a combination of 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene
(iPr) and the corresponding 7-azaindole derivative (HL1–4),
were prepared and characterized. The complexes of the composition
of [Au(iPr)(Ln)], where n = 1–4
for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3), and 3-iodo-7-azaindole
(4), were further evaluated for their in vitro anticancer
and anti-inflammatory activities. The results showed that complexes
(1–4) behave as considerably cytotoxic
against human ovarian cancer cell line A2780 (with IC50 ≈ 4–9 μM) and cisplatin-resistant
cell line A2780R (with IC50 ≈ 7–12 μM,
except for 2 with IC50 > 25 μM),
providing
significantly higher cytotoxicity than the anticancer drug cisplatin. Moreover, they also revealed a relatively good
selectivity over normal cells (MRC-5), with selectivity index values
of SI > 2.5. Complex 4 showed the ability to interact
with l-cysteine and reduced glutathione at normal extracellular
and intracellular levels, respectively. Complex 4 was
further studied for its cellular effects in A2780 cells using flow
cytometry. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor
NF-κB and secretion of TNF-α were evaluated, showing that
complex 4 reveals comparable effects as the inflammatory
drug auranofin.