(Amino)cyclophosphazenes as Multisite Ligands for the Synthesis of Antitumoral and Antibacterial Silver(I) Complexes

The reactivity of the multisite (amino)cyclotriphosphazene ligands, [N₃P₃(NHCy)₆] and [N₃P₃(NHCy)₃(NMe₂)₃], has been explored in order to obtain silver(I) metallophosphazene complexes. Two series of cationic silver(I) metallophosphazenes were obtained and characterized: [N₃P₃(NHCy)₆{AgL}](TfO) [n = 2, L = PPh₃ (2), PPh₂Me (4); n = 3, L = PPh₃ (3), PPh₂Me (5), TPA (TPA = 1,3,5-triaza-7-phosphaadamantane, 6)] and nongem-trans-[N₃P₃(NHCy)₃(NMe₂)₃{AgL}](TfO) [n = 2, L = PPh₃ (7), PPh₂Me (9); n = 3, L = PPh₃ (8), PPh₂Me (10)]. 5, 7, and 9 have also been characterized by single-crystal X-ray diffraction, thereby allowing key bonding information to be obtained. Compounds 2-6, 9, and 10 were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria strains. Both the IC₅₀ and MIC values revealed excellent biological activity for these metal complexes, compared with their precursors and cisplatin and also AgNO₃ and silver sulfadiazine, respectively. Both IC₅₀ and MIC values are among the lowest values found for any silver derivatives against the cell lines and bacterial strains used in this work. The structure-activity relationships were clear. The most cytotoxic and antimicrobial derivatives were those with the triphenylphosphane and [N₃P₃(NHCy)₆] ligands. A significant improvement in the activity was also observed upon a rise in the number of silver atoms linked to the phosphazene ring.