Ruthenium(II) Complexes of Thiosemicarbazones: The First Water‐Soluble Complex with pH‐Dependent Antiproliferative Activity

Abstract

Abstract Two ruthenium(II) complexes of 2‐acetylpyridine N 4 , N 4 ‐dimethylthiosemicarbazone (HL 1 ) and phenanthrenequinone thiosemicarbazone (HL 2 ), namely [Ru II Cl(L 1 )(PPh 3 ) 2 ] ( 1 ) and [Ru II Cl(L 2 )(PPh 3 ) 2 ] ( 2 ), have been synthesised and characterised by IR, UV/Vis and NMR spectroscopy, electrospray mass spectrometry, cyclic voltammetry and X‐ray crystallography. In addition, the X‐ray crystal structure of [Ru III Cl 2 (L 2 )PPh 3 ] · dmso · 1.25H 2 O ( 3· dmso · 1.25H 2 O) is reported. The reaction of [Ru II Cl 2 (dmso) 4 ] with HL 1 and 1,3,5‐triaza‐7‐phosphaadamantane (PTA) gives the highly water‐soluble complex [Ru II Cl(L 1 )(HPTA) 2 ]Cl 2 · C 2 H 5 OH · H 2 O ( 4· C 2 H 5 OH · H 2 O) ( S 25°C ≥ 250 mg/mL), which has been fully characterised. Complex 4 shows strong antiproliferative effects in low micromolar concentrations in the ovarian carcinoma cell line 41M (IC 50 = 0.87 μ M ) and more moderate activity in the breast cancer cell line SK‐BR‐3 (IC 50 = 39 μ M ). The activity of the compound is 6.5‐ and 5.4‐times higher at pH = 6.0 than at pH = 7.4 in the non‐small cell lung cancer cell line A549 and the colon carcinoma cell line HT‐29 (GI 50 = 24 and 8.0 μ M at pH = 6.0 for A549 and HT‐29, respectively). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)