The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC50 val Show more
The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC50 values of 50 nM (lymphoma cells) and 500 nM (leukemia cells), respectively (Mes < iPr). The compounds exclusively induce apoptosis (50 nM to 5 μM) instead of necrosis in common malignant blood cells (leukemia cells) and do not affect non-malignant leucocytes. Remarkably, the complexes not only overcome resistances against the well-established cytostatic etoposide, cytarabine, daunorubicin, and cisplatin but also promote a synergistic effect of up to 182% when used with daunorubicin. The present results demonstrate that gold(I) bis(1,2,3-triazol-5-ylidene) complexes are highly promising and easily modifiable anticancer metallodrugs. Show less
Gold(I) complexes with phosphane and thiotetrazolate ligands were prepared and investigated as a new type of bioactive gold metallodrugs. The complexes triggered very efficient inhibition of t Show more
Gold(I) complexes with phosphane and thiotetrazolate ligands were prepared and investigated as a new type of bioactive gold metallodrugs. The complexes triggered very efficient inhibition of the enzyme thioredoxin reductase (TrxR), which is an important molecular target for gold species. Strong cytotoxic effects were observed in MDA-MB-231 breast adenocarcinoma and HT-29 colon carcinoma cells, and the complexes also caused strong effects in vincristine resistant Nalm-6 leukemia cells. Cellular uptake studies showed elevated cellular gold levels for complexes containing a triphenylphosphane ligand, whereas trifurylphosphane analogues accumulated at significantly lower cellular concentrations.
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