Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands

• Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were developed.
• [RuCl(η6-p-cym)(1,10-phenanthroline-5,6-dione)][PF6] was the most potent compound.
• [RuCl(η6-p-cym)(1,10-phenanthroline-5,6-dione)][PF6] was selective towards the T. brucei.
• Both proteins and DNA are likely to be targeted by this potential metallodrugs.

Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η6-p-cym)(L)][PF6], where p-cym = 1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro-phenanthroline, 5. In the other two complexes [RuCl2(η6-p-cym)(L′)], the metal is coordinated to a monodentate ligand L′, where L′ is phenanthridine, 2, or 9-carbonylanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower Trypanosoma brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 = 1.26 ± 0.78 μM) and antiparasitic (IC50 = 0.19 ± 0.05 μM) agent, showing high selectivity towards the parasites (selectivity index > 100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.

Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were developed. [RuCl(η6-p-cym)(1,10-phenanthroline-5,6-dione)][PF6] was the most potent antitumoral (IC50 = 1.26 μM) and antiparasitic (T. brucei, IC50 = 0.19 μM) agent, showing high selectivity towards the parasites (selectivity index > 100). DNA and ubiquitin were studied as potential targets for the obtained compounds.Figure optionsDownload as PowerPoint slide