In comparison with Ru-II-arene compounds, the medicinal potential of homologous Ru-II-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(kappa(3)-tpm)(PPh3)(2)]Cl (1) to afford [RuCl(kappa(3)-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 degrees 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.

Anticancer ruthenium(II) tris(pyrazolyl)methane complexes with bioactive co-ligands

Gobbo, Alberto
Primo
;
Biancalana, Lorenzo;Zacchini, Stefano;Dyson, Paul J;Marchetti, Fabio
Ultimo
2022-01-01

Abstract

In comparison with Ru-II-arene compounds, the medicinal potential of homologous Ru-II-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(kappa(3)-tpm)(PPh3)(2)]Cl (1) to afford [RuCl(kappa(3)-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 degrees 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.
2022
Gobbo, Alberto; Pereira, Sarah A P; Biancalana, Lorenzo; Zacchini, Stefano; Saraiva, M Lúcia M F S; Dyson, Paul J; Marchetti, Fabio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1157865
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