Electron-transfer activated metal-based anticancer drugs
Electron-transfer activated metal-based anticancer drugs
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DOI：
10.1016/j.ica.2006.12.005
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发表时间：
2008-05
影响因子：
2.8
通讯作者：
E. Reisner;V. Arion;B. Keppler;A. Pombeiro
中科院分区：
文献类型：
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作者：
E. Reisner;V. Arion;B. Keppler;A. Pombeiro
铂（II）为基础的抗癌药物在临床上发挥了重要作用，今天，和一些与其他金属的配合物是在目前的发展作为有前途的抗肿瘤药物。可能最突出的非铂金属为基础的药物是那些钌。已经应用了各种策略来设计具有改进的毒理学特征的新型药物，其中之一涉及制备惰性高氧化态的金属络合物[例如Pt（IV）、Ru（III）]。三种铂（IV）和两种钌（III）药物已经进入临床试验阶段。理想情况下，低氧选择性药物被递送到目标环境中，而无需通过金属中心的取代反应进行预先还原或主要转化。已经提出了（选择性）还原以通过形成活性物质来激活前药，所述活性物质更容易与靶标反应并最终导致细胞凋亡。因此，铂（IV）和钌（III）细胞毒素的电化学行为的调查和初步的结构-性能关系的建立是目前的重要性。在此，我们提出了最近的结果在该领域的金属为中心的电子转移激活Ru（III），Pt（IV）和Co（III）药物的设计和靶向策略，预测在水介质中的氧化还原电位，不稳定性和增强的反应性与潜在的生物靶点还原后，和电化学参数和抗癌活性之间的相关性。
Platinum(II)-based anticancer drugs play an essential role in the clinic today, and a number of coordination compounds with other metals are in current development as promising antitumor drugs. Probably the most prominent non-platinum metal-based drugs are those of ruthenium. Various strategies have been applied for the design of novel drugs with an improved toxicological profile, and one of them involves the preparation of metal complexes in inert high oxidation states [e.g. Pt(IV), Ru(III)]. Three platinum(IV) and two ruthenium(III) drugs have already reached clinical trials. Ideally, hypoxia-selective drugs are delivered to the target environment without prior reduction or major transformation via substitution reactions at the metal center. A (selective) reduction has been proposed to activate the prodrugs by formation of active species, which react with the target more readily and lead ultimately to apoptosis. Investigations on the electrochemical behavior of platinum(IV) and ruthenium(III) cytotoxins and the establishment of preliminary structure–property relationships are therefore of current importance. Herein, we present recent results in the field of metal-centered electron-transfer activated Ru(III), Pt(IV) and Co(III) drugs with regard to design and targeting strategies, prediction of redox potentials in aqueous medium, labilization and enhanced reactivity with potential biological targets upon reduction, and correlations between electrochemical parameters and anticancer activity.