Figure 1.
Schematic representations of gold(I) complexes used as anti-inflammatory drugs.
A: Sodium aurothiomalate (Myochrysin, sodium {(2-carboxy-1-carboxylatoethyl)thiolato}gold(I)); B: Aurothioglucose (Solganol, {(2 S,3R,4 S,5 S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-oxane-2-thiolato}gold(I)); C: Auranofin (Ridaura, triethylphosphine-(2,3,4,6-tetra-O-acetyl-1-D-thiopyranosato-S)gold(I)).
Figure 2.
Schematic representation of the prepared gold(I) complexes 1–9.
Table 1.
1H and 13C NMR coordination shifts (Δδ = δcomplex–δligand; ppm) of calculated for 1–9.
Figure 3.
Molecular structure of [Au(L1)(PPh3)] (1).
The molecular structure of 1 showing the atom numbering scheme. Non-hydrogen atoms are displayed as ellipsoids at the 50% probability level.
Figure 4.
Molecular structure of [Au(L3)(PPh3)] (3).
The molecular structure of 3 showing the atom numbering scheme. Non-hydrogen atoms are displayed as ellipsoids at the 50% probability level.
Table 2.
In vitro cytotoxicity of complexes 1–9 and cisplatin against MCF7 and HOS cancer cell lines.
Figure 5.
vitro cytotoxicity against selected cancer cell lines for complexes 4–6 and cisplatin. The cells were exposed to the employed complexes for 24 h. Measurements were performed in triplicate and each cytotoxicity experiment was repeated three times. The given IC50±SE (µM) values represent an arithmetic mean. The asterisk (*) denotes significant difference (ANOVA, p<0.05) between 4–6 and cisplatin.
Table 3.
In vitro cytotoxicity of complexes 4–6 and cisplatin against a panel of cancer cell lines.
Figure 6.
Effects of the Au(I) complexes 1–9, reference drug Auranofin, [AuCl(PPh3)], AuCl, PPh3 and HL1–9 on LPS-induced TNF-α (A) and IL-1β (B) secretion.
The cells were pretreated with the tested compounds (300 nM) or the vehicle (0.1% DMSO) only. After 1 h of the incubation, the inflammatory response was induced by LPS [except for the control cells (CTRL)]. The secretion was determined 24 h after the LPS addition. The results are expressed as means±SE of three independent experiments. Significant difference in comparison to: *vehicle-treated cells (p<0.05), **vehicle-treated cells (p<0.01), ***vehicle-treated cells (p<0.001).
Figure 7.
Effects of the Au(I) complexes 2 and 7, and reference drug Auranofin on gene expression of TNF-α (A) and IL-1β (B).
THP-1 macrophages were pretreated with complexes 2, 7 and Auranofin at the concentration of 300 nM or the vehicle (0.1% DMSO) only. After 1 h of the incubation, the inflammatory response was induced by LPS [except for the control cells (CTRL)]. After 2 h, the level of TNF-α and IL-1β mRNA was evaluated by RT-qPCR. The amount of cytokine mRNA was normalised to β-actin mRNA. The results are expressed as means±SE of three independent experiments. A.U. = arbitrary unit. Significant difference in comparison to: *vehicle-treated cells (p<0.05), **vehicle-treated cells (p<0.01).
Figure 8.
The results of the ESI-MS study of complex 1 (A) and 6 (B) solutions and interacting systems involving the mixture of physiological levels of cysteine and reduced glutathione and complex 1 (C) or complex 6 (D).