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金属配合物作为有前途的生物医学应用试剂。

Metal Complexes as Promising Agents for Biomedical Applications.

机构信息

Faculty of Chemistry, Belarusian State University, Minsk, Belarus.

Research Institute for Physico-Chemical Problems of the Belarusian State University, Minsk, Belarus.

出版信息

Curr Med Chem. 2020;27(31):5213-5249. doi: 10.2174/0929867326666190417143533.

Abstract

BACKGROUND

In this review article, a brief overview of novel metallotherapeutic agents (with an emphasis on the complexes of essential biometals) promising for medical application is presented. We have also focused on the recent work carried out by our research team, specifically the development of redox-active antimicrobial complexes of sterically hindered diphenols with some essential biometals (copper, zinc, nickel).

RESULTS

The complexes of essential metals (manganese, iron, cobalt, nickel, copper, zinc) described in the review show diverse in vitro biological activities, ranging from antimicrobial and antiinflammatory to antiproliferative and enzyme inhibitory. It is necessary to emphasize that the type of organic ligands in these metal complexes seems to be responsible for their pharmacological activities. In the last decades, there has been a significant interest in synthesis and biological evaluation of metal complexes with redox-active ligands. A substantial step in the development of these redox-active agents is the study of their physicochemical and biological properties, including investigations in vitro of model enzyme systems, which can provide evidence on a plausible mechanism underlying the pharmacological activity. When considering the peculiarities of the pharmacological activity of the sterically hindered diphenol derivatives and their nickel(II), copper(II) and zinc(II) complexes synthesized, we took into account the following: (i) all these compounds are potential antioxidants and (ii) their antimicrobial activity possibly results from their ability to affect the electron-transport chain.

CONCLUSION

We obtained novel data demonstrating that the level of antibacterial and antifungal activity in the series of the above-mentioned metal-based antimicrobials depends not only on the nature of the phenolic ligands and complexing metal ions, but also on the lipophilicity and reducing ability of the ligands and metal complexes, specifically regarding the potential biotargets of their antimicrobial action - ferricytochrome c and the superoxide anion radical. The combination of antibacterial, antifungal and antioxidant activity allows one to consider these compounds as promising substances for developing therapeutic agents with a broad spectrum of activities.

摘要

背景

在这篇综述文章中,我们简要概述了具有医学应用前景的新型金属治疗剂(重点是必需生物金属的配合物)。我们还专注于我们研究团队最近的工作,特别是具有空间位阻二酚的氧化还原活性抗菌配合物的开发,这些配合物与一些必需生物金属(铜、锌、镍)形成配合物。

结果

本综述中描述的必需金属(锰、铁、钴、镍、铜、锌)配合物具有多样化的体外生物活性,从抗菌和抗炎到抗增殖和酶抑制。有必要强调的是,这些金属配合物中的有机配体类型似乎与其药理活性有关。在过去几十年中,人们对具有氧化还原活性配体的金属配合物的合成和生物学评价产生了浓厚的兴趣。这些氧化还原活性试剂的发展的一个重要步骤是研究其物理化学和生物学性质,包括对模型酶系统的体外研究,这可以为药理学活性的可能机制提供证据。在考虑空间位阻二酚衍生物及其合成的镍(II)、铜(II)和锌(II)配合物的药理活性的特殊性时,我们考虑了以下几点:(i) 所有这些化合物都是潜在的抗氧化剂;(ii) 它们的抗菌活性可能是由于它们影响电子传递链的能力。

结论

我们获得了新的数据,表明上述金属基抗菌剂系列的抗菌和抗真菌活性水平不仅取决于酚配体和配位金属离子的性质,还取决于配体和金属配合物的亲脂性和还原能力,特别是关于其抗菌作用的潜在生物靶点-细胞色素 c 铁和超氧阴离子自由基。抗菌、抗真菌和抗氧化活性的结合使这些化合物成为开发具有广泛活性的治疗剂的有前途的物质。

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