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Author Spotlight: Assessing the Impact of Novel Iron Chelators on Cancer Cell Metabolism
Published on: February 23, 2024
Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(II) sandwich complexes
Alberto Gobbo1, Sarah A P Pereira2,3, Fátima A R Mota2
1University of Pisa, Department of Chemistry and Industrial Chemistry, Via G. Moruzzi 13, I-56124 Pisa, Italy. fabio.marchetti@unipi.it.
Abstract:
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.
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