Cytotoxicity of arene ruthenium metalla-rectangles incorporating bis-pyridyl diimide linkers

• Ten arene ruthenium metalla-rectangles were synthesized and characterized.
• The biological activity of the arene ruthenium metalla-cycles was explored.
• They display cancer cell selectivity and high antiproliferative activity.

A series of tetranuclear arene ruthenium complexes of the general formula [Ru4(p-cymene)4(μ2-L)2(μ4-OO∩OO)2][CF3SO3]4 (L1 = N,N’-bis(4-pyridylmethyl)-pyromellitic diimide, L2 = N,N’-bis(4-pyridylmethyl)-naphthalene diimide) were obtained from the corresponding dinuclear arene ruthenium complexes Ru2(p-cymene)2(μ4-OO∩OO)Cl2 (OO∩OO = oxalato (oxa), 2,5-dioxido-1,4-benzoquinonato (dobq), 2,5-dihydroxy-3-phenyl-1,4-benzoquinonato (dhpb), 2,5-dichloro-1,4-benzoquinonato (dClbq), 2,5-dioxido-3-undecyl-1,4-benzoquinonato (dubq), 2,5-dihydroxy-3,6-diphenyl-1,4-benzoquinonato (dhdb), 5,8-dioxido-1,4-naphtoquinonato (donq)) by reaction with the bidentate ligands (L1 and L2) and silver trifluoromethanesulfonate. The antiproliferative activity of the tetranuclear arene ruthenium metalla-rectangles was evaluated on cancerous (A2780 and A2780cisR) and non-cancerous (HEK293) cell lines, showing in all cases cancer cell selectivity. In general, the metalla-rectangles obtained with L2 are more potent than those incorporating L1, and with the exception of [Ru4(p-cymene)4(μ2-L1)2(μ4-dClbq)2][CF3SO3]4, they are all more active than cisplatin on the cisplatin resistant A2780cisR cell line.

The antiproliferative activity of ten arene ruthenium metalla-rectangles was evaluated on cancerous (A2780 and A2780cisR) and non-cancerous (HEK293) cells, showing in all cases cancer cell selectivity, low micromolar cytotoxicity and higher activity than cisplatin on a cancer cell line that has acquired resistance to cisplatin.Figure optionsDownload as PowerPoint slide