Cytotoxicity of ruthenocene-containing β-diketones.

BACKGROUND Ferrocene-containing β-diketones and cisplatin, [(NH(3))(2)PtCl(2)], possess strong antineoplastic activity. No information is available regarding the anticancer activity of the corresponding ruthenocene complexes. This study examined the cytotoxicity of stable ruthenocene-containing β-diketones. The results were related to the cytotoxicity of cisplatin and the ease of ruthenium electrochemical oxidation. MATERIALS AND METHODS The ruthenocene-containing β-diketones RcCOCH(2)COR where Rc=Ru(II)(C(5)H(5))(C(5)H(4)) and R=CF(3) (1), CH(3) (2), Ph=C(6)H(5) (3) and Fc=Fe(II)(C(5)H(5))(C(5)H(4)) (4) were tested for cytotoxicity against HeLa (human cervix epithelioid) cancer, COR L23 (human large cell lung carcinoma) and the platinum-resistant CoLo 320DM (human colorectal) and COR L23/CPR cancer cell lines. Cell survival was measured by means of the colourimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay. RESULTS The 50% cell growth inhibition (IC(50)) values of 1-4 towards the cells ranged between 8.2 and 84.6 μmol dm(-3), with 1 being the most cytotoxic complex. Drug activity was directly proportional to the electron density on the ruthenium centre as well as the oxidation potential of the ruthenium core but inversely proportional to the pK(a) of the β-diketones. The strongest activity was observed against the COR L23 cell line, and the weakest activity against COR L23 CPR. CONCLUSION A drug activity-structural relationship exists for ruthenocene-containing β-diketones in that drugs with the lowest electron density on the ruthenium centre are more cytotoxic. Compounds with larger ruthenium oxidation potentials and stronger acid strength (i.e. smaller pK(a) values) are more cytotoxic.