Unusual DNA binding modes for metal anticancer complexes.
Unusual DNA binding modes for metal anticancer complexes.
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DOI：
10.1016/j.biochi.2009.03.017
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发表时间：
2009-10
期刊：
影响因子：
3.9
通讯作者：
Sadler, Peter J.
中科院分区：
文献类型：
--
作者：
Pizarro, Ana M.;Sadler, Peter J.
DNA被认为是许多金属类药物的主要目标。例如，铂类抗癌药物可以在DNA上形成特异性病变，从而诱导细胞凋亡。新的铂类药物可以被设计成具有与DNA相互作用的新模式，例如三核铂配合物BBR3464。也可以设计惰性铂（IV）前药，在黑暗中无毒，但在某些波长的光照射下致命。这就产生了新的DNA损伤，这些损伤不像顺铂引起的那样容易修复，并为一种新型光激活化疗提供了基础。最后，新出现的钌（II）有机金属配合物不仅与DNA协调结合，而且通过在其多功能结构中引入扩展芳烃环引发的h键和疏水相互作用与DNA结合。有趣的是，锇（钌的重同系物）与DNA的反应不同，但也会产生高细胞毒性的有机金属复合物。
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 hydrophibic 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.
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