Department of Chemistry, University of the Free State, Bloemfontein 9300, Republic of South Africa.
Anticancer Res. 2012 Jul;32(7):2915-8.
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.
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.
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.
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.
二茂铁基β-二酮和顺铂，[(NH(3))(2)PtCl(2)]，具有很强的抗肿瘤活性。目前尚无关于相应的钌茂配合物的抗癌活性的信息。本研究检测了稳定的钌茂基β-二酮的细胞毒性。结果与顺铂的细胞毒性和钌电化学氧化的容易程度有关。
测试了钌茂基β-二酮 RcCOCH(2)COR，其中 Rc=Ru(II)(C(5)H(5))(C(5)H(4))，R=CF(3)（1）、CH(3)（2）、Ph=C(6)H(5)（3）和 Fc=Fe(II)(C(5)H(5))(C(5)H(4))（4）对 HeLa（人宫颈上皮样）癌、COR L23（人大细胞肺癌）以及铂耐药 CoLo 320DM（人结直肠）和 COR L23/CPR 癌细胞系的细胞毒性。通过比色 3-(4,5-二甲基噻唑-2-基)-二苯基四氮唑溴化物（MTT）测定法测量细胞存活率。
1-4 对细胞的 50%细胞生长抑制（IC(50)）值在 8.2 至 84.6 μmol dm(-3)之间，其中 1 是最具细胞毒性的配合物。药物活性与钌中心的电子密度以及钌核的氧化电位成正比，但与β-二酮的 pK(a)成反比。对 COR L23 细胞系观察到最强的活性，对 COR L23 CPR 观察到最弱的活性。
对于含有钌茂基的β-二酮存在药物活性-结构关系，即钌中心电子密度最低的药物具有更高的细胞毒性。具有更大的钌氧化电位和更强的酸强度（即更小的 pK(a)值）的化合物具有更高的细胞毒性。
