👤 Pereira SAP

Ruthenium-based complexes have been suggested as promising anticancer drugs exhibiting reduced general toxicity compared to platinum-based drugs. In particular, Ru(η⁶-arene)(PTA)Cl₂ (PTA = 1,3,5-triaza-7-phosphaadamantane), or RAPTA, complexes have demonstrated efficacy against breast cancer by suppressing metastasis, tumorigenicity, and inhibiting the replication of the human tumor suppressor gene BRCA1. However, RAPTA compounds have limited cytotoxicity, and therefore comparatively high doses are required. This study explores the activity of a series of RAPTA-like ruthenium(II) arene compounds against MCF-7 and MDA-MB-231 breast cancer cell lines and [Ru(η⁶-toluene)(PPh₃)₂Cl]⁺ was identified as a promising candidate. Notably, [Ru(η⁶-toluene)(PPh₃)₂Cl]Cl was found to be remarkably stable and highly cytotoxic, and selective to breast cancer cells. The minor groove of DNA was identified as a relevant target. Show less

Title: Anticancer ruthenium(II) tris(pyrazolyl)methane complexes with bioactive co-ligands. Abstract: In comparison with RuII-arene compounds, the medicinal potential of homologous RuII-tpm compounds [tpm = tris(pyrazolyl)methane] is underexplored. Pyridine, 4-pyridinemethanol and four functionalized pyridines, synthesized from the esterification of 4-pyridinemethanol with bioactive carboxylic acids (i.e., ethacrynic acid, ibuprofen, flurbiprofen and naproxen), react with the precursor [RuCl(κ3-tpm)(PPh3)2]Cl (1) to afford [RuCl(κ3-tpm)(PPh3)(L)]Cl (2-7, L = pyridine ligand), in 78-91% yields. All products were fully characterized by HR-ESI mass spectrometry, IR and multinuclear NMR spectroscopy and the solid-state structures of two of the complexes, i.e. where L = pyridine and 4-pyridinemethanol, were ascertained by single crystal X-ray diffraction. The {Ru-tpm-PPh3} assembly is stable in D2O and in biological medium (DMEM) at 37 °C, with a tendency to slowly dissociate the pyridine ligand. The antiproliferative activity of the complexes was assessed on the cancerous A2780 and A2780cisR cell lines, and the nontumoral HEK 293T cell line; moreover inhibition assays were carried out on the complexes towards COX-2 and GSTP1 enzymes. Show less