Tris(pyrazolyl)methane (tpm), 2,2,2-tris(pyrazolyl)ethanol (tpm(OH)) and its esterification derivatives with ibuprofen and flurbiprofen (tpm(IBU) and tpm(FLU)) were used as ligands to obtain complexes of the type [Fe(tpm(X))(2)]Cl-2 (1-4). The tpm(IBU) and tpm(FLU) ligands and corresponding complexes 3 and 4 were characterized by IR and multinuclear NMR spectroscopy, and the structure of tpm(IBU) was elucidated by single crystal X-ray diffraction. Complexes 1-4 were also assessed for their behaviour in aqueous media (solubility in D2O, octanol/water partition coefficient, stability in physiological-like conditions). The antiproliferative activity of ligands and complexes was determined on A2780, A2780cis and A549 cancer cell lines and the non-cancerous HEK 293T and BJ cell lines. The ligands and complexes were investigated for their ability to inhibit COX-2 (cyclooxygenase) and HNE (4-hydroxynonenal) enzymes. Complexes 3 and 4 exhibited cytotoxicity that may be attributed predominantly to their bioactive fragments, while DNA binding and enhancement of ROS production do not appear to play any significant role.
Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(ii) sandwich complexes
Gobbo, Alberto;Rocchi, Dario;Guelfi, Massimo;Biver, Tarita;Donati, Chiara;Zacchini, Stefano;Dyson, Paul J.;Marchetti, Fabio
2024-01-01
Abstract
Tris(pyrazolyl)methane (tpm), 2,2,2-tris(pyrazolyl)ethanol (tpm(OH)) and its esterification derivatives with ibuprofen and flurbiprofen (tpm(IBU) and tpm(FLU)) were used as ligands to obtain complexes of the type [Fe(tpm(X))(2)]Cl-2 (1-4). The tpm(IBU) and tpm(FLU) ligands and corresponding complexes 3 and 4 were characterized by IR and multinuclear NMR spectroscopy, and the structure of tpm(IBU) was elucidated by single crystal X-ray diffraction. Complexes 1-4 were also assessed for their behaviour in aqueous media (solubility in D2O, octanol/water partition coefficient, stability in physiological-like conditions). The antiproliferative activity of ligands and complexes was determined on A2780, A2780cis and A549 cancer cell lines and the non-cancerous HEK 293T and BJ cell lines. The ligands and complexes were investigated for their ability to inhibit COX-2 (cyclooxygenase) and HNE (4-hydroxynonenal) enzymes. Complexes 3 and 4 exhibited cytotoxicity that may be attributed predominantly to their bioactive fragments, while DNA binding and enhancement of ROS production do not appear to play any significant role.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.