Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes as anticancer drug candidates

Abstract

Due to the increasing impact of cancer on worldwide mortality, more and more attention is being devoted to the investigation of novel anticancer strategies. Among these, chemotherapy plays a key role in fighting cancer. This explains the increasing engagement of both pharmaceutical industry and academia towards the discovery of new chemotherapeutic agents. Over the recent years, metal-based drugs have attracted much attention due to their atypical physico-chemical properties compared to organic molecules. After the approval of cisplatin as a chemotherapeutic agent in 1978, several types of metal-based drugs have been explored. Among them, Ru-based anticancer drug candidates have become a central subject in this research field. However, most of the Ru-based compounds investigated over the last two decades express their cytotoxicity with a mechanism of action involving, among others, a ligand-exchange mechanism. In this Review, we give a complete overview of a specific class of antiproliferative ruthenium complexes, namely coordinatively saturated and substitutionally inert Ru(II) polypyridyl complexes. This implies that the cytotoxicity observed comes from the entire complex and not from a ligand-exchange. In this Review, we are presenting monomeric and dimeric Ru(II) polypyridyl complexes, which have been found to be toxic to cancer cells. More specifically, the monomeric Ru(II) polypyridyl complexes are analysed considering their direct interaction or not with DNA as cause of cell death, while dimeric Ru(II) polypyridyl complexes, are classified according to their biological targets. Very importantly, the cellular targets of these complexes are discussed in detail. Indeed, several targets were identified and different mechanisms of action were suggested.

A Maltol‐Containing Ruthenium Polypyridyl Complex as a Potential Anticancer Agent

“…The Ru III complexes KP1019, KP1339 (referred as IT‐139 recently) and NAMI‐A have entered clinical trials as anticancer drugs, while TLD‐1433, a substitutionally inert Ru II polypyridyl complex, recently entered phase II clinical trial as a photosensitizer for photodynamic therapy (PDT) . Inert Ru polypyridyl complexes hold tremendous potential as chemotherapeutic agents against cancer . Recently, we reported the in‐depth biological investigation of a very promising Ru II polypyridyl complex carrying a semiquinonate ligand ([Ru(DIP) 2 (sq)](PF 6 )) (Figure , DIP=4,7‐diphenyl‐1,10‐phenantroline, sq=semiquinonate) .…”

The Antimicrobial Activity of Mononuclear Ruthenium(II) Complexes Containing the dppz Ligand

“…Thereh as been recent interest in developing kineticallyi nert polypyridylruthenium(II) complexesa st herapeutic agents, [1][2][3][4][5] with complexesc ontainingt he dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligand attracting particular attention. [6][7][8] Barton andc oworkerse stablishedt hat[ Ru(bpy) 2 (dppz)] 2 + (bpy = 2,2'-bipyridine)a nd [Ru(phen) 2 (dppz)] 2 + (phen = 1,10-phenanthroline) strongly bind DNAb yi ntercalation,a nd becauset hese complexes exhibitn egligibleb ackground emission in aqueouss olution butd isplay strong luminescence upon DNAb inding, they arenow knownas"molecularlight switches".…”

Synthesis, Characterization, and Biological Evaluation of Red-Absorbing Fe(II) Polypyridine Complexes

“…To the obtained solution, an aqueous saturated solution of NH 4 PF 6 (5 mL) was added. The crude product, which precipitated as a PF 6 Fe(4,7-Diphenyl-1,10-phenanthroline-4 ,4"-disulfonic acid) 3 Na 6 (2): Disodium-4,7-Diphenyl-1,10phenanthroline-4 ,4"-disulfonic acid (600 mg, 1.08 mmol) and FeCl 2 ·4H 2 O (61 mg, 0.31 mmol) were suspended in ethanol (50 mL) under nitrogen atmosphere and the mixture was refluxed for 14 h. After that, the solution was cooled down and undissolved residue was removed via filtration. The crude product was dissolved in a H 2 O/CH 3 CN solution (50 mL) and fractionated precipitated by adding dropwise Et 2 O.…”