Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(II) sandwich complexes

Dalton Trans. 2024 Aug 13;53(32):13503-13514. doi: 10.1039/d4dt00920g.

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.

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal* / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Drug Screening Assays, Antitumor
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology
  • Humans
  • Ibuprofen / chemistry
  • Ibuprofen / pharmacology
  • Ligands
  • Methane / analogs & derivatives
  • Methane / chemistry
  • Methane / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Ligands
  • Antineoplastic Agents
  • Coordination Complexes
  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Ferrous Compounds
  • Methane
  • Cyclooxygenase 2
  • Aldehydes
  • Reactive Oxygen Species
  • Ibuprofen