Thiophenolato-bridged dinuclear arene ruthenium complexes: a new family of highly cytotoxic anticancer agents.
New cationic diruthenium complexes of the type [(arene)(2)Ru(2)(SPh)(3)](+), arene being C(6)H(6), p-(i)PrC(6)H(4)Me, C(6)Me(6), C(6)H(5)R, where R = (CH(2))(n)OC(O)C(6)H(4)-p-O(CH(2))(6)CH(3) or (CH(2))(n)OC(O)CH=CHC(6)H(4)-p-OCH(3) and n = 2 or 4, are obtained from the reaction of the corresponding precursor [(arene)RuCl(2)](2) and thiophenol and isolated as their chloride salts. The complexes have been fully characterised by spectroscopic methods and the solid state structure of [(C(6)H(6))(2)Ru(2)(SPh)(3)](+), crystallised as the hexafluorophosphate salt, has been established by single crystal X-ray diffraction. The complexes are highly cytotoxic against human ovarian cancer cells (cell lines A2780 and A2780cisR), with the IC(50) values being in the submicromolar range. In comparison the analogous trishydroxythiophenolato compounds [(arene)(2)Ru(2)(S-p-C(6)H(4)OH)(3)]Cl (IC(50) values around 100 μM) are much less cytotoxic. Thus, it would appear that the increased antiproliferative effect of the arene ruthenium complexes is due to the presence of the phenyl or toluyl substituents at the three thiolato bridges.
Gras
Michaël
M
Institut de Chimie, Université de Neuchâtel, Case postale 158, CH-2009, Neuchâtel, Switzerland.
Therrien
Bruno
B
Süss-Fink
Georg
G
Zava
Olivier
O
Dyson
Paul J
PJ
D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*
D000475:Alkenes; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D013455:Sulfur; D012428:Ruthenium