摘要
背景:伴随化学疗法的固有问题需要开发新的抗癌方法。通过与蛋白质和非规范DNA结构(例如G-四联体)的相互作用,以及通过改变细胞内氧化还原平衡,可以通过新机制破坏癌性细胞机制的化合物的开发,是当今激烈研究的焦点。在这种情况下,贵金属Pt和Au的有机金属化合物已成为显着的实验治疗剂。这篇综述提供了Pt(II)和Au(III)环金属化合物与含有强C-M键的螯合环的概述,以改进化合物在配体交换反应和生物还原方面的稳定性。此外,通过修饰阴离子环金属化或辅助配体,可以容易地调整这些性质。对于C ^ N,C ^ N ^ C,C ^ N ^ N和C ^ N ^ S铂(II)和金(III)螯合物的合成和作为抗癌剂的生物学作用机制已经有了特别的关注。 方法:对同行评议的研究文献进行了化学和药物数据库的结构化搜索。检索的文件的质量使用标准工具进行评估。仔细审查和描述了所述化合物的合成以及化学和生物学性质。使用概念框架概述了这些发现。 结果:在这篇综述中,我们收录了155篇论文,大部分来源于对铂(II)和金(III)化合物的合成和生物模式的高影响力论文。其中,有17篇论文着重介绍了具有药用性质的铂和金化合物的使用,主要集中在配位化合物。在51篇论文中概述了各种金属(如Fe,Ru,Ti)的有机金属化合物的合成和药物性质。这些化合物包括茂金属,金属茂,金属羰基,金属卡宾(例如N-杂环卡宾)和炔基络合物。讨论了铂(II)(46篇论文)和金(III)(44篇论文)的C ^ N,C ^ N ^ C,C ^ N ^ N和C ^ N ^ S螯合物的合成,稳定性和开发治疗化合物的优势。我们力争从早期开始就展示C ^ N,C ^ N ^ C,C ^ N ^ N和C ^ N ^ S铂(II)和金(III)钳状络合物在其合成和生物模式方面的一致发展。到最近的调查结果
关键词: 有机金属,环金属,金,铂,癌症治疗,抗癌剂
Current Medicinal Chemistry
Title:Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives
Volume: 25 Issue: 4
关键词: 有机金属,环金属,金,铂,癌症治疗,抗癌剂
摘要: Background: The inherent problems accompanying chemotherapy necessitate the development of new anticancer approaches. The development of compounds that can disrupt cancerous cellular machinery by novel mechanisms, via interactions with proteins and non-canonical DNA structures (e.g. G-quadruplexes), as well as by alteration of the intracellular redox balance, is nowadays focus of intense research. In this context, organometallic compounds of the noble metals Pt and Au have become prominent experimental therapeutic agents. This review provides an overview of the Pt(II) and Au(III) cyclometalated compounds with a chelating ring containing a strong C-M σ -bond to improve the stability of the compounds with respect to ligand exchange reactions and biological reduction. Furthermore, these properties can be easily tuned by modification of either the anionic cyclometalated or the ancillary ligands. Special focus has been set to C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological mechanisms of action as anticancer agents. Methods: A structured search of both chemical and medicinal databases for peerreviewed research literature has been conducted. The quality of retrieved papers was appraised using standard tools. The synthesis as well as the chemical and biological properties of the described compounds were carefully reviewed and described. The findings were outlined using a conceptual framework.
Results: In this review we included 155 papers, the majority originating from high-impact papers on the synthesis and biological modes of platinum(II) and gold(III) compounds. Among them, 17 papers were highlighted to give an introduction to the use of Pt and Au compounds with medicinal properties, mainly focussing on coordination compounds. The synthesis and medicinal properties of organometallic compounds of various metals (such as Fe, Ru, Ti) were outlined in 51 papers. These compounds included metallocenes, metallo- arenes, metallo-carbonyls, metallo-carbenes (e.g. N-heterocyclic carbenes), and alkynyl complexes. The C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum( II) (46 papers) and gold(III) (44 papers) were discussed concerning their synthesis, stability and advantages to develop therapeutic compounds. We strove to show the consistent development of C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological modes from the early beginnings to the most recent findings.
Conclusion: This review supplies a profound overview of the development of organometallic compounds for medicinal purposes, setting special focus to the synthesis and stability of C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum(II) and gold(III) and their use as anticancer agents.
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Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives, Current Medicinal Chemistry 2018; 25 (4) . https://dx.doi.org/10.2174/0929867324666170529125229
DOI https://dx.doi.org/10.2174/0929867324666170529125229 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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