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