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基于核酸修饰新策略的抗肿瘤铂配合物设计

郑小辉1,2, 夏立新1*, 毛宗万2*

化学进展 ›› 2016, Vol. 28 ›› Issue (7) :1029-1038

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化学进展 ›› 2016, Vol. 28 ›› Issue (7) :1029-1038 DOI: 10.7536/PC160112
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基于核酸修饰新策略的抗肿瘤铂配合物设计

    郑小辉1,2, 夏立新1*, 毛宗万2*
作者信息 +

The New Anticancer Platinum Complex Designed on the Basis of Nucleic Acid

  • Zheng Xiaohui1,2, Xia Lixin1*, Mao Zongwan2*
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文章历史 +

摘要

肿瘤已成为严重威胁人类健康的重大疾病之一。以顺铂为首的铂类抗肿瘤药物一直是化疗首选药物。但是长期用药导致的一系列的毒副作用如肾毒性、耳毒性和耐药性等极大地限制了铂类配合物的发展与应用。本文针对目前铂类药物所处形势重点综述了新一代铂类药物的设计研发方法:(1)研发具有新颖结构的铂类药物,例如经过改造的反式铂类配合物、多核铂类配合物、Pt(Ⅳ)配合物等;(2)发展新的抗肿瘤靶点,例如以G-四螺旋DNA(G4-DNA)为靶点,为寻找更有效的铂类抗肿瘤药物提供新的思路。同时通过列举最新研究成果,分析药物的抗肿瘤机理及在克服顺铂耐药性机理方面的研究进展,提出铂类药物的设计研发方法,让读者了解铂类抗肿瘤药物的发展历程和未来的发展趋势。

Abstract

Tumor is one of the serious diseases which greatly threaten human's health. Therefore, the large amount of innovative anticancer drugs have been discovered and created. Among these anticancer drugs, cis-platinum and its analogs are some of the most effective chemotherapeutic agents in clinical use, particularly in the treatment of testicular and ovarian cancers. Unfortunately, they have several major drawbacks, such as cumulative toxicities of nephrotoxicity and ototoxicity, inherent or treatment-induced resistance. This has provided the urgency and motivation for developing novel platinum complexes with high antitumor effect and low toxic side effect on normal cells. This review highlights some methods on the development of the novel platinum complexes:(1) developing the platinum complex with new structure, like trans-platinum complex, multinuclear platinum complex, Pt(Ⅳ) complex; (2) developing new anticancer target, such as G-quadruplex (G4) DNA. By consideration of the anticancer mechanism of the drugs and the tolerance of cis-platinum, the prospect provides new ways to develop novel platinum complexes with high antitumor effect and low toxic side effect on normal cells. This review highlights recent progress of the platinum complexes as anticancer drugs and discuss their future potential in the medical fields.

Contents
1 Introduction
2 Nucleic acid
2.1 Duplex DNA
2.2 G-quadruplex DNA
3 Platinum complexes targeting duplex DNA
3.1 Classical platinum(Ⅱ) complexes
3.2 Trans-platinum(Ⅱ) complexes
3.3 Multi-nuclear platinum(Ⅱ) complexes
3.4 Platinum(Ⅳ) complexes
4 Platinum complexes targeting G-quadruplex DNA
4.1 Mono-nuclear platinum(Ⅱ) complexes
4.2 Multi-nuclear platinum(Ⅱ) complexes
5 Conclusion and outlook

Graphical abstract

关键词

核酸 / 抗肿瘤 / 铂配合物 / G-四螺旋DNA / 双螺旋DNA

Key words

nucleic acid / anticancer / platinum complex / G-quadruplex DNA / duplex DNA

引用本文

引用格式 ▾
郑小辉, 夏立新, 毛宗万. 基于核酸修饰新策略的抗肿瘤铂配合物设计[J]. 化学进展, 2016, 28(7): 1029-1038 DOI:10.7536/PC160112
Zheng Xiaohui, Xia Lixin, Mao Zongwan. The New Anticancer Platinum Complex Designed on the Basis of Nucleic Acid[J]. Progress in Chemistry, 2016, 28(7): 1029-1038 DOI:10.7536/PC160112

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