Biological activities of pyrenyl-derived thiosemicarbazone half-sandwich complexes

• Mononuclear half-sandwich complexes with pyrenyl-derived thiosemicarbazone ligands.
• The single-crystal X-ray structure analysis of two representative complexes is presented.
• The antiproliferative activity of all complexes has been evaluated in vitro (IC50 < 10 μM).
• Cytotoxic complexes on cancer cell lines with some selectivity.

Pyrenyl-derived thiosemicarbazone half-sandwich complexes of the types [(η6-p-MeC6H4Pri)Ru(Ln)Cl]+ and [(η5-C5Me5)M(Ln)Cl]+ (M = Rh, Ir; L1 = pyrenecarboxaldehyde-3-thiosemicarbazone, L2 = pyrenecarboxaldehyde-4-methyl-3-thiosemicarbazone, L3 = pyrenecarboxaldehyde-4-phenyl-3-thiosemicarbazone) were synthesized and isolated as their chloride salts by reacting in THF the dinuclear complexes [(η6-p-MeC6H4Pri)2Ru2(μ-Cl)2Cl2] and [(η5-C5Me5)2M2(μ-Cl)2Cl2] with the corresponding Ln ligand. All complexes were isolated in good yields and were fully characterized by spectroscopic methods, including single-crystal X-ray structure analyses of the ruthenium complex [(η6-p-MeC6H4Pri)Ru(L1)Cl]Cl and the rhodium derivative [(η5-C5Me5)Rh(L2)Cl]Cl. The complexes were found to have IC50 values in the micromolar range against cancer cells (A-549, DU-145, HeLa, MCF-7), with a lower cytotoxicity in the noncancerous human HEK-293 embryonic kidney cells. The best two candidates, the rhodium derivatives [(η5-C5Me5)Rh(L1)Cl]Cl and [(η5-C5Me5)Rh(L3)Cl]Cl, show anticancer activities comparable to doxorubicin. These two complexes were further evaluated, showing an inhibition of the cell cycle at the G2/M and subG1 stages.

A series of pyrenyl-derived thiosemicarbazone half-sandwich complexes has been synthesized and characterized. The cytotoxicity of all complexes has been established using cancerous and noncancerous cell lines. The rhodium derivatives appeared to be the most active compounds, having IC50 values in the micromolar range.Figure optionsDownload as PowerPoint slide