FIGURE SUMMARY
Title

Anti-tumoural [NHC(thiolato)]Au(I) complexes derived from HIF-1α inhibitor AC1-004 target the mitochondrial redox system and show antiangiogenic effects in vivo

Authors
Schleser, S.W., Köhler, L.H.F., Riethmüller, F., Reich, S., Fertig, R., Schlotte, L., Seib, J., Goller, A., Begemann, G., Kempe, R., Schobert, R.
Source
Full text @ Chempluschem
Fig. 1

Molecular structure of complex 9 b as thermal ellipsoid representations at the 50 % probability level (H atoms omitted). Selected bond lengths [Å] and angles [°]: C1−Au 1.990, Au−S 2.292, Au−S−C2 106.09, C1−Au−S 177.76.

Fig. 2

Fluorescence-based DCFH-DA assays showed the reactive oxygen species (ROS) levels in 518A2 melanoma cells treated with 5, 10 and 20 μm of test compounds 9 a–e, 10 a–c, 17, 20, 21, AC1-004, YC-1, auranofin and the positive control hydrogen peroxide (H2O2, 1 μm) compared with solvent treated cells set to 100 %. The values are means±SD from at least three independent experiments.

Fig. 3

Effect of compounds 9 a–e, 10 a–c, 17, AC1-004, YC-1, (10 μm) and auranofin (5 μm) on the cell distributions in the different cell cycle phases of 518A2 melanoma cells after 24 h of treatment. Values±SD of two independent experiments were derived from at least 10000 counted cells with solvent-treated control set to 100 %.

Fig. 4

Immunofluorescence images of the actin cytoskeleton (green) and the nuclei (blue) of 518A2 melanoma cells after treatment with compounds 9 a–c, 10 a–c, 17, AC1-004, YC-1, (10 μm), 9 d–e (5 μm) or auranofin (1 μm) for 24 h. Images are representative of at least two independent experiments. Scale bars correspond to 50 μm, magnification 640×.

Fig. 5

Confocal imaging of 518A2 melanoma cells treated with 25 μm of cyclopropene derivatives 20 or 21 and BDP-FL-tetrazine for bioorthogonal labelling (green), or with MitoTracker® Red CM-H2XRos (violet), or DAPI (blue). Images are representative of at least two independent experiments. Scale bars correspond to 50 μm, magnification 640×. Pearson correlation coefficient (PCC) was calculated for colocalised nuclei and mitochondria using the coloc2 function (image J). The bottom scheme shows the general cycloaddition reaction of cyclopropenes 20 and 21 with BPD-FL-tetrazine to give fluorescent diazines.

Fig. 6

At least 21 zebrafish larvae each were treated with test compounds 9 c, 10 a–c, 17, YC-1 (10 μm), 9 d (5 μm), 9 a, 9 b, 9 e, AC1-004 and auranofin (1 μm) for 48 h. To estimate the antiangiogenic effect, the SIV (subintestinal vessel) area was quantified via ImageJ and quoted as the mean±SD with solvent-treated fish set to 100 %. Significance is given as n.s.: >0.05; *: <0.05; ***: <0.001; ****: <0.0001, One-way ANOVA with Dunnett's multiple comparison test (GraphPad Prism 9).

Acknowledgments
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