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Unusual DNA binding modes for metal anticancer complexes

机译:金属抗癌复合物的异常DNA结合模式

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摘要

DNA is believed to be the primary target for many metal-based drugs. For example, platinum-based anticancer drugs can form specific lesions on DNA that induce apoptosis. New platinum drugs can be designed that have novel modes of interaction with DNA, such as the trinuclear platinum complex BBR3464. Also it is possible to design inert platinum(IV) pro-drugs which are non-toxic in the dark, but lethal when irradiated with certain wavelengths of light. This gives rise to novel DNA lesions which are not as readily repaired as those induced by cisplatin, and provides the basis for a new type of photo-activated chemotherapy. Finally, newly emerging ruthenium(II) organometallic complexes not only bind to DNA coordinatively, but also by H-bonding and hydrophobic interactions triggered by the introduction of extended arene rings into their versatile structures. Intriguingly osmium (the heavier congener of ruthenium) reacts differently with DNA but can also give rise to highly cytotoxic organometallic complexes.
机译:DNA被认为是许多基于金属的药物的主要靶标。例如,基于铂的抗癌药可以在诱导凋亡的DNA上形成特异性损伤。可以设计具有与DNA相互作用的新模式的新铂药物,例如三核铂复合物BBR3464。还可以设计惰性的铂(IV)前药,该药在黑暗中无毒,但在某些波长的光照射下却具有致命性。这产生了不如顺铂诱导的那样容易修复的新型DNA损伤,并为新型光活化化学疗法提供了基础。最后,新出现的钌(II)有机金属配合物不仅能与DNA配位结合,而且还可以通过将扩展的芳烃环引入其通用结构而引发的H键和疏水相互作用。有趣的是,((较重的钌同类物)与DNA的反应不同,但也会产生高度细胞毒性的有机金属配合物。

著录项

  • 来源
    《Biochimie》 |2009年第10期|1198-1211|共14页
  • 作者单位

    Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK;

    Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    DNA; metallodrug; organometallic complex; transition metals; photoactivation;

    机译:脱氧核糖核酸;金属药物有机金属配合物过渡金属;光活化;

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