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]aneS(3) half-sandwich complexes of the type [Ru([9]aneS(3))Cl(N-N)][CF3SO3] and [Ru([9]aneS(3))(dmso-S)(N-N)][CF3SO3](2) (5-15, N-N = substituted bpy or 2 x 1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS(3))Cl(3,3'-H(2)dcbpy)][CF3SO3] (9) (3,3'-H(2)dcbpy = 3,3'-dicarboxy-2,2'-bipyridine), [Ru([9]aneS(3))Cl(4,4'-dmobpy)][CF3SO3] (13) (4,4'-dmobpy = 4,4'-dimethoxy-2,2-bipyridine), and [Ru([9]aneS(3))Cl(1-MeIm)(2)][CF3SO3] (15) (1-Melm = 1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(eta(6)-arene)Cl(N-N)][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]aneS(3))Cl(en)][CF3SO3] (1, en = ethylenediamine), [Ru([9]aneS(3))Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS(3))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]aneS(3). This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin). (C) 2008 Elsevier Inc. All rights reserved.