Redox-active antineoplastic ruthenium complexes with indazole: Correlation of in vitro potency and reduction potential
Redox-active antineoplastic ruthenium complexes with indazole: Correlation of in vitro potency and reduction potential
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DOI：
10.1021/jm0490742
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发表时间：
2005-04-21
影响因子：
7.3
通讯作者：
Keppler, BK
中科院分区：
文献类型：
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作者：
Jakupec, MA;Reisner, E;Keppler, BK
抗肿瘤Ru(III)络合物通常被认为是前药，通过还原而被激活。因此，在一系列同源的Ru(III)络合物中，细胞毒力预计会随着还原的日益容易而增加。合成了通式为[(RuCl(6-n))-Cl-III(Ind)(N)]((3-n)-)(n=0-4；ind=吲唑；反离子=Hind(+)或Cl-)和反式[(RuCl2)-Cl-II(Ind)(4)]的配合物，并对其进行了电化学表征。Level的参数化法预测，吲唑与氯的比例越大，还原电位越高，循环伏安法也证实了这一点。这些配合物对结肠癌细胞(SW480)和卵巢癌细胞(CH1)的体外抗肿瘤活性差异超过2个数量级，并按下列顺序递增：[(RuCl6)-Cl-III](3-)<；[(RuCl4)-Cl-III(Ind)(2)](-)<；[(RuCl5)-Cl-III(Ind)](2-)
Antineoplastic ruthenium(III) complexes are generally regarded as prodrugs, being activated by reduction. Within a homologous series of ruthenium(III) complexes, cytotoxic potency is therefore expected to increase with increasing ease of reduction. Complexes of the general formula [(RuCl(6-n))-Cl-III(ind)(n)]((3-n)-) (n = 0-4; ind = indazole; counterions = Hind(+) or Cl-) and the compound trans- [(RuCl2)-Cl-II(ind)(4)] have been prepared and characterized electrochemically. Lever's parametrization method predicts that a higher indazole-to-chloride ratio results in a higher reduction potential, which is confirmed by cyclic voltammetry. In vitro antitumor potencies of these complexes in colon cancer cells (SW480) and ovarian cancer cells (CH1) vary by more than 2 orders of magnitude and increase in the following rank order: [(RuCl6)-Cl-III](3-) < [(RuCl4)-Cl-III(ind)(2)](-) < [(RuCl5)-Cl-III(ind)](2-)