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Updated: Apr 15, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Structure-Related Mode-of-Action Differences of Anticancer Organoruthenium Complexes with β-Diketonates
Sara Seršen1, Jakob Kljun1, Kushtrim Kryeziu2
1†Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Abstract:
A series of organoruthenium(II) chlorido complexes with fluorinated O,O-ligands [(η(6)-p-cymene)Ru(F3C-acac-Ar)Cl] (1a-6a) and their respective 1,3,5-triaza-7-phosphaadamantane (pta) derivatives [(η(6)-p-cymene)Ru(F3C-acac-Ar)pta]PF6 (1b-6b) were synthesized and fully characterized in both solution and solid state. All complexes were inactive against nonmalignant keratinocytes but displayed variable activity against cancer cell models (ovarian, osteosarcoma). Compounds with a ligand containing the 4-chlorophenyl substituent (6a and 6b) exhibited the strongest anticancer effects. Despite a marginally lower cellular Ru accumulation compared to the chlorido complexes, pta analogues showed higher activity especially in the osteosarcoma model. Reduction of glutathione levels by buthionine sulfoximine (BSO) significantly enhanced the activity of all compounds with the most pronounced effects being observed for the pta series resulting in IC50 values down to the nanomolar range. While all chlorido complexes potently induce reactive oxygen species, DNA damage, and apoptosis, the respective pta compounds widely lacked ROS production but blocked cell cycle progression in G0/G1 phase.
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