Silver-Based Terpyridine Complexes as Antitumor Agents

Silver-Based Terpyridine Complexes as Antitumor Agents

Author: Chemistry – A European Journal

Silver compounds are interesting as potential anticancer agents due to their reduced toxicity to healthy cells. However, research on silver complexes with terpyridine-based ligands is limited, despite the potential for these compounds to combine the properties of the metal and the ligands’ ability to bind to DNA.

M. Concepción Gimeno, CSIC-Universidad de Zaragoza, Spain, José M. López-de-Luzuriaga, Universidad de La Rioja, Logroño, Spain, and colleagues have synthesized a family of silver complexes using 4-substituted terpyridines and tetra-2-pyridinylpyrazine as ligands. To obtain terpyridine-based complexes, the team reacted the desired ligand with AgBF4 in diethyl ether. Terpyridine-based complexes with an ancillary triphenylphosphine or trimethylphosphine ligand were synthesized from the corresponding terpyridine ligand and [Ag(S)PPh3]BF4 or freshly prepared Ag(S)PMe3]BF4 (S = solvent). For the complexes containing tetra-2-pyridinylpyrazine, the team also reacted the ligand with [Ag(S)PPh3]BF4 or Ag(S)PMe3]BF4.

The team studied the antitumor properties of the synthesized compounds and established a structure-activity relationship. The highest selectivity was found with trimethylphosphine as an ancillary ligand (example pictured). The researchers observed high cytotoxicity against several tumor cells and a high selectivity index between tumor and healthy cells. Additionally, they evaluated the possible mechanism through which these derivatives may interact with DNA using absorption spectral titration experiments. They found that the compounds can interact with CT-DNA through moderate intercalation and promote apoptosis via the mitochondrial pathway. These findings suggest that silver derivatives have potential for the development of new anticancer agents.


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