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金属抗癌配合物的异常DNA结合模式。

Unusual DNA binding modes for metal anticancer complexes.

作者信息

Pizarro Ana M, Sadler Peter J

机构信息

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

出版信息

Biochimie. 2009 Oct;91(10):1198-211. doi: 10.1016/j.biochi.2009.03.017. Epub 2009 Apr 1.

Abstract

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 photoactivated 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.

摘要

DNA被认为是许多金属基药物的主要靶点。例如,铂基抗癌药物可在DNA上形成特定损伤,从而诱导细胞凋亡。可以设计出与DNA具有新型相互作用模式的新型铂药物,如三核铂配合物BBR3464。此外,还可以设计惰性铂(IV)前药,它们在黑暗中无毒,但在特定波长的光照射下具有致死性。这会产生新型的DNA损伤,这些损伤不像顺铂诱导的损伤那样容易修复,为新型光活化化疗提供了基础。最后,新出现的钌(II)有机金属配合物不仅通过配位与DNA结合,还通过在其通用结构中引入扩展芳烃环引发的氢键和疏水相互作用与DNA结合。有趣的是,锇(钌的较重同系物)与DNA的反应不同,但也能产生高细胞毒性的有机金属配合物。

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