Synthesis, characterization and in vitro anticancer activity of highly cytotoxic trithiolato diruthenium complexes of the type [(η6-p-MeC6H4iPr)2Ru2(μ2-SR1)2(μ2-SR2)]+ containing different thiolato bridges

Highly cytotoxic diruthenium trithiolato complexes of the type [(η6-p-MeC6H4Pri)2Ru2(μ2-SR)3]+: synthesis, characterization, molecular structure and in vitro anticancer activity

“…This ratio is superior to 100 in normal resting cells, whereas in various situations of oxidative stress this ratio is reported to decrease to values between 10 and 1. 17 For the present series of complexes [(Z 6 -p-MeC 6 H 4 Pr i ) 2 -Ru 2 (m 2 -SR) 3 ] + containing thiophenolato ligands with ortho and meta substituents, the catalytic activity for the oxidation of GSH to GSSG was also analyzed by NMR spectroscopy. [26][27][28] A depletion of GSH could therefore affect the ability of cancer cells to cope with oxidation damage.…”

Insights into the in vitro Anticancer Effects of Diruthenium‐1

“…[25] However,a lthough ad ecrease in GSH levels with increasing DiRu-1 concentrationw as observed in vitro and in vivo, [24] no directc orrelation between cytotoxicity and catalytic activity for the oxidationofG SH wasfound. [19,21,22] Ab iodistribution study of DiRu-1 showed ruthenium to be present in the tumor and particularly in the excretory organs, but not in the brain, suggesting that it cannotp ass through the brain-blood barrier (BBB). In human breast cancerc ells MCF-7 and BT-549, DiRu-1w as found to exhibit antiproliferative and cytotoxic effects, to stimulate the expression and phosphorylationo fp 53, and to modulate the expression of MAP kinases.…”

Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

“…An endpoint colorimetric MTT assay (MTT=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) was used instead of IncuCyte observations, because it allowed to test the nonadherent and semi‐adherent cell lines, such as THP‐1, HL‐60 and HepG2 (Table ). This, or similar assays, have been widely used previously to assess the antiproliferative activity of metal complexes, including Ru‐arene‐thiolato dimers . All the cell lines were treated for 72 h with 50±5 μ m Ru (verified by atomic absorption spectroscopy, see the Experimental Section).…”

“…Although such complexes predominantly contain N, O, or P donor ligands, a notable series of thiolato‐bridged Ru II arene dimers has been developed by Furrer, Süss‐Fink and co‐workers . In particular, trithiolato dimers, such as those shown in Figure , are stable under biological conditions, and are highly cytotoxic (IC 50 values in nanomolar range) in common cancer cell lines . The absence of easily hydrolysable ligands in these dimers (Figure ) means that they are likely to act by a different mechanism to those of classical Pt II drugs, or the Ru drugs that have entered clinical trials, which also undergo rapid ligand exchange reactions .…”

“…A proposed mechanism is based on their efficient cellular uptake (probably by passive diffusion through cell membranes due to the hydrophobic nature of the complexes), followed by catalytic oxidation of cellular thiols by oxygen, leading to production of reactive oxygen species that cause cell death . Generally, these complexes were not selective for a particular cell type, although in one instance lower toxicity in lung cancer cells compared with breast cancer, or leukemia cells was observed . The reasons for such selectivity were not further explored.…”