Synthesis and anticancer activity evaluation of η5-C5(CH3)4R ruthenium complexes bearing chelating diphosphine ligands

The complexes [RuCp*(PP)Cl] (Cp* = C5Me5; [1], PP = dppm; [4], PP = Xantphos), [RuCp#(PP)Cl] (Cp# = C5Me4(CH2)5OH; [2], PP = dppm; [5], PP = Xantphos) and [RuCp*(dppm)(CH3CN)][SbF6] [3] were syn- thesized and evaluated in vitro as anticancer agents. Compounds 1–3 gave nanomolar IC50 values against normoxic A2780 and HT-29 cell lines, and were also tested against hypoxic HT-29 cells, maintaining their high activity. Complex 3 yielded an IC50 value of 0.55 ± 0.03 μM under a 0.1% O2 concentration

Structure–Activity Relationships of Targeted Ru^II(η⁶‑<i>p</i>‑Cymene) Anticancer Complexes with Flavonol-Derived Ligands

Ru^II(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized Ru^II(η⁶-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multitargeted anticancer agents. To validate this concept, studies on the mode of action of the complexes were conducted which indicated that they form covalent bonds to DNA, have only minor impact on the cell cycle, but inhibit CDK2 and topoisomerase IIα in vitro. The cytotoxic activity was determined in human cancer cell lines, resulting in very low IC₅₀ values as compared to other Ru^II(arene) complexes and showing a structure–activity relationship dependent on the substitution pattern of the flavonol ligand. Furthermore, the inhibition of cell growth correlates well with the topoisomerase inhibitory activity. Compared to the flavonol ligands, the Ru^II(η⁶-<i>p</i>-cymene) complexes are more potent antiproliferative agents, which can be explained by potential multitargeted properties

Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (N,N)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC50 values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for in vivo studies