%0 Journal Article
%T Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(II) sandwich complexes.
%A Gobbo A
%A Pereira SAP
%A Mota FAR
%A Sinenko I
%A Glinkina K
%A Rocchi D
%A Guelfi M
%A Biver T
%A Donati C
%A Zacchini S
%A Saraiva MLMFS
%A Dyson PJ
%A Marchetti F
%J Dalton Trans
%V 53
%N 32
%D 2024 Aug 13
%M 39072444
%F 4.569
%R 10.1039/d4dt00920g
%X Tris(pyrazolyl)methane (tpm), 2,2,2-tris(pyrazolyl)ethanol (tpmOH) and its esterification derivatives with ibuprofen and flurbiprofen (tpmIBU and tpmFLU) were used as ligands to obtain complexes of the type [Fe(tpmX)2]Cl2 (1-4). The tpmIBU and tpmFLU ligands and corresponding complexes 3 and 4 were characterized by IR and multinuclear NMR spectroscopy, and the structure of tpmIBU 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.