Anticancer ruthenium(II) tris(pyrazolyl)methane complexes with bioactive co-ligands.

Area of Science:

• Organometallic Chemistry
• Medicinal Inorganic Chemistry
• Coordination Chemistry

Background:

• Ruthenium(II)-arene compounds are well-studied in medicinal chemistry.
• Ruthenium(II)-tris(pyrazolyl)methane (tpm) complexes remain relatively underexplored for therapeutic applications.
• There is a need to investigate novel metal-based compounds for cancer treatment and enzyme inhibition.

Purpose of the Study:

• To synthesize and characterize novel Ruthenium(II)-tpm complexes incorporating functionalized pyridine ligands.
• To evaluate the stability of these complexes in aqueous and biological media.
• To assess the antiproliferative activity against cancer cell lines and inhibitory effects on COX-2 and GSTP1 enzymes.

Main Methods:

• Synthesis of Ruthenium(II)-tpm complexes using a [RuCl(κ³-tpm)(PPh₃)₂]Cl precursor and various pyridine ligands.
• Characterization using HR-ESI mass spectrometry, IR, and multinuclear NMR spectroscopy.
• Solid-state structure determination by single crystal X-ray diffraction for selected complexes.
• Stability studies in D₂O and DMEM at 37 °C.
• Antiproliferative assays on A2780, A2780cisR, and HEK 293T cell lines.
• Enzyme inhibition assays against COX-2 and GSTP1.

Main Results:

• Six novel Ruthenium(II)-tpm complexes were synthesized in high yields (78-91%).
• Complexes demonstrated stability in aqueous and biological media, with slow dissociation of the pyridine ligand.
• Preliminary biological evaluation showed antiproliferative activity and enzyme inhibition potential.

Conclusions:

• The synthesized Ruthenium(II)-tpm complexes represent a promising new class of metallodrug candidates.
• The {Ru-tpm-PPh₃} core offers a stable scaffold for developing compounds with potential anticancer and enzyme-inhibiting properties.
• Further investigation into the structure-activity relationship is warranted.