Sixteen hydrazinyl-thiazolo arene ruthenium complexes of the general formula [(η(6)-p-cymene)Ru(N,N'-hydrazinyl-thiazolo)Cl]Cl were synthesized. All complexes were tested in vitro for their antiproliferative activity on three tumor cell lines (HeLa, A2780, and A2780cisR) and on a noncancerous cell line (HFL-1). A superior cytotoxic activity of the ruthenium complexes as compared to cisplatin and oxaliplatin, on both cisplatin-sensitive and cisplatin resistant ovarian cancer cells, was observed. In addition, the biological activity of two selected derivatives was evaluated using microarray gene expression assay and ingenuity pathway analysis. p53 signaling was identified as an important pathway modulated by both arene ruthenium compounds. New activated molecules such as FAS, ZMAT3, PRMT2, BBC3/PUMA, and PDCD4, whose overexpressions are correlated with overcoming resistance to cisplatin therapy, were also identified as potential targets. Moreover, the arene ruthenium complexes can be used in association with cisplatin to prevent cisplatin resistance development and synergistically to induce cell death in ovarian cancer cells.

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The synthesis and characterization of three metalla-rectangles of the general formula [Ru4(η6-p-cymene)4(μ4-clip)2(μ2-Lanthr)2][CF3SO3]4 (Lanthr: 9,10-bis(3,3’-ethynylpyridyl) anthracene; clip = oxa: oxalato; dobq: 2,5-dioxido-1,4-benzoquinonato; donq: 5,8-dioxido-1,4-naphthoquinonato) are presented. The molecular structure of the metalla-rectangle [Ru4(η6-p-cymene)4(μ4-oxa)2(μ2-Lanthr)2]4+ has been confirmed by the single-crystal X-ray structure analysis of [Ru4(η6-p-cymene)4(μ4-oxa)2(μ2-Lanthr)2][CF3SO3]4 · 4 acetone (A2 · 4 acetone), thus showing the anthracene moieties to be available for reaction with oxygen. While the formation of the endoperoxide form of Lanthr was observed in solution upon white light irradiation, the same reaction does not occur when Lanthr is part of the metalla-assemblies.