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氮茚类化合物:细胞毒性过渡金属配合物的合适配体。

Azaindoles: Suitable ligands of cytotoxic transition metal complexes.

机构信息

Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic.

Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic.

出版信息

J Inorg Biochem. 2019 Aug;197:110695. doi: 10.1016/j.jinorgbio.2019.110695. Epub 2019 Apr 24.

Abstract

This minireview is devoted to the complexes of various transition metals, which contain azaindole ring coordinated to the metal centre, and whose cytotoxicity was studied. We decided to overview this interesting group of coordination compounds with the aim to highlight various structural types of complexes depending on the metal centre (i.e., Pt, Pd, Ru, Ir or Au) and type of the used co-ligand(s). The presented complexes are also reviewed in context of their toxicity, selectivity and processes connected with their mechanism of action. Some of complexes were also studied on in vivo models showing promising results comparable with the commonly used anticancer drug cisplatin. It can be deduced from the herein overviewed literature data regarding transition metal complexes containing azaindoles as ligands, that at least a few of them may represent suitable and promising candidates in the field of anticancer therapy. As one of the examples, the cis-[PtI(2Me4Cl-7aza)] complex (2Me4Cl-7aza = 2-methyl-4-chloro-7-azaindole) should be mentioned, which showed considerably higher in vitro cytotoxicity than cisplatin, the ability to overcome both the acquired and natural resistance of human cancer cells in comparison with the biological action of cisplatin, different mechanism of action than cisplatin and comparable in vivo anticancer activity with cisplatin.

摘要

这篇综述专门介绍了含有与金属中心配位的氮茚环的各种过渡金属配合物,并且研究了它们的细胞毒性。我们决定综述这组有趣的配位化合物,重点介绍不同结构类型的配合物,取决于金属中心(即 Pt、Pd、Ru、Ir 或 Au)和所用辅助配体的类型。所介绍的配合物还根据其毒性、选择性以及与其作用机制相关的过程进行了综述。其中一些配合物也在体内模型中进行了研究,结果显示出与常用抗癌药物顺铂相当的有前景的结果。从本文综述的关于含有氮茚作为配体的过渡金属配合物的文献数据可以推断,其中至少有几种可能是抗癌治疗领域的合适且有前途的候选物。例如,顺式-[PtI(2Me4Cl-7aza)] 配合物(2Me4Cl-7aza=2-甲基-4-氯-7-氮茚)就值得一提,它显示出比顺铂高得多的体外细胞毒性,能够克服人癌细胞的获得性和天然耐药性,与顺铂的生物学作用相比,具有不同的作用机制,并且与顺铂相比,在体内具有相当的抗癌活性。

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