Half-sandwich RuII[9]aneS3 complexes structurally similar to antitumor-active organometallic piano-stool compounds: Preparation, structural characterization and in vitro cytotoxic activity

The preparation, structural characterization, and chemical behavior in aqueous solution of a series of new Ru[9]aneS3 half-sandwich complexes of the type [Ru([9]aneS3)Cl(NN)][CF3SO3] and [Ru([9]aneS3)(dmso-S)(NN)][CF3SO3]2 (5–15, NN = substituted bpy or 2 × 1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS3)Cl(3,3′-H2dcbpy)][CF3SO3] (9) (3,3′-H2dcbpy = 3,3′-dicarboxy-2,2′-bipyridine), [Ru([9]aneS3)Cl(4,4′-dmobpy)][CF3SO3] (13) (4,4′-dmobpy = 4,4′-dimethoxy-2,2′-bipyridine), and [Ru([9]aneS3)Cl(1-MeIm)2][CF3SO3] (15) (1-MeIm = 1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(η6-arene)Cl(NN)][PF6]. Three chloro compounds (5, 9, 15) were tested in vitro for cytotoxic activity against two human cancer cell lines in comparison with the previously described [Ru([9]aneS3)Cl(en)][CF3SO3] (1, en = ethylenediamine), [Ru([9]aneS3)Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS3)Cl(dmso-S)2][CF3SO3] (3). Only the ethylenediamine complex 1 showed some antiproliferative activity, ca. one order of magnitude lower than the reference organometallic half-sandwich compound RM175 that contains biphenyl instead of [9]aneS3. This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin).