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Cytotoxic platinum coordination compounds. DNA binding agents

机译：细胞毒性铂配位化合物。 DNA结合剂

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摘要

Despite the widespread use of antineoplastic platinum drugs, a number of accompanying disadvantages exist. In connection with attempts to circumvent these problems, new platinum compounds have been prepared and mechanisms underlying their biological activity have been extensively investigated. These mechanistic investigations involve research focused on understanding interactions of platinum agents with DNA since DNA binding and recognition of DNA modified by these metallodrugs are the important processes responsible for their anticancer properties. In this review, we discuss how various classes of platinum(II) complexes, which can interact with DNA by coordination, intercalation and other noncovalent modes of binding or by a combination of these DNA binding modes, can alter the cellular response induced by conventional platinum drugs. We describe that these alterations can be achieved by changing: (i) the nature and structure of the DNA lesion induced; (ii) conformational alterations induced in DNA by these lesions; and (iii) various cellular signaling pathways initiated by platinum DNA damage. We anticipate that summarization of the results on DNA binding of cytotoxic platinum compounds may help to shed light on their potency and will make it possible to create new strategies to design rationally new anticancer platinum compounds and/or combine platinum drugs with other cytotoxic agents. (C) 2017 Elsevier B.V. All rights reserved.
机译：尽管抗肿瘤铂药物的广泛使用，但存在许多伴随的缺点。为了克服这些问题，已经制备了新的铂化合物，并且已经广泛研究了其生物学活性的基础机理。这些机械研究涉及集中于理解铂试剂与DNA相互作用的研究，因为DNA结合和被这些金属药物修饰的DNA的识别是负责其抗癌特性的重要过程。在这篇综述中，我们讨论了各种类型的铂（II）配合物如何通过配位，嵌入和其他非共价结合方式或这些DNA结合方式的组合与DNA相互作用，如何改变常规铂诱导的细胞应答毒品。我们描述了这些改变可以通过改变来实现：（i）诱导的DNA损伤的性质和结构； （ii）这些损伤在DNA中诱导的构象改变； （iii）铂DNA损伤引发的各种细胞信号通路。我们预期，细胞毒性铂化合物与DNA结合的结果的总结可能有助于阐明其功效，并将有可能创造新策略，以合理设计新的抗癌铂化合物和/或将铂药物与其他细胞毒性剂联合使用。 （C）2017 Elsevier B.V.保留所有权利。

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  • 来源
    《Coordination chemistry reviews》 |2017年第11期|2-31|共30页
  • 作者

    Brabec Viktor; Hrabina Ondrej; Kasparkova Jana;

  • 作者单位

    Acad Sci Czech Republ, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic;

    Acad Sci Czech Republ, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic|Palacky Univ, Fac Sci, Dept Biophys, Slechtitelu 27, Olomouc 78371, Czech Republic;

    Acad Sci Czech Republ, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic;

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

    Platinum; DNA binding; Cross-links; Photoactivation; Cytotoxicity;

    机译：铂;DNA结合;交联;光活化;细胞毒性;

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