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金、铂和钯的抗癌金属-N-杂环卡宾配合物。

Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium.

机构信息

Department of Chemistry, State Key Laboratory of Synthetic Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong.

Department of Chemistry, State Key Laboratory of Synthetic Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong.

出版信息

Curr Opin Chem Biol. 2018 Apr;43:30-36. doi: 10.1016/j.cbpa.2017.10.014. Epub 2017 Nov 11.

Abstract

Transition metal compounds are a rich source for anticancer drug development. Judicious application of coordination ligands is a critical success factor in the design of effective anti-tumor compounds. N-heterocyclic carbenes (NHC) are stable ligands that have strong donor strengths in stabilizing metal ions and versatility in structural modifications to provide diverse scaffolds for biological molecular targeting. Remarkable advances have been achieved in the development of metal NHC complexes as anticancer as well as theranostic agents. NHC complexes of gold, platinum and palladium have been designed to elicit potent cancer cell cytotoxicity, effective anti-tumor activities in animal models as well as selective binding to molecular targets (e.g. protein thiols, DNA G-quadraplexes, mismatched DNA). The mechanisms of action of some of these complexes have been elucidated.

摘要

过渡金属化合物是开发抗癌药物的丰富来源。明智地应用配位体是设计有效抗肿瘤化合物的关键成功因素。氮杂环卡宾(NHC)是稳定的配体,在稳定金属离子方面具有很强的供电子能力,并且在结构修饰方面具有多功能性,可以为生物分子靶向提供多种支架。在开发作为抗癌和治疗诊断双重用途的金属 NHC 配合物方面已经取得了显著进展。金、铂和钯的 NHC 配合物被设计用来引起强烈的癌细胞细胞毒性,在动物模型中具有有效的抗肿瘤活性,以及对分子靶标(例如蛋白质硫醇、DNA G-四链体、错配 DNA)的选择性结合。其中一些配合物的作用机制已经阐明。

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