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用于对抗病原微生物的钌配合物。全面综述。

Ruthenium Complexes in the Fight against Pathogenic Microorganisms. An Extensive Review.

作者信息

Munteanu Alexandra-Cristina, Uivarosi Valentina

机构信息

Department of General and Inorganic Chemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.

出版信息

Pharmaceutics. 2021 Jun 13;13(6):874. doi: 10.3390/pharmaceutics13060874.

DOI:10.3390/pharmaceutics13060874
PMID:34199283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8232020/
Abstract

The widespread use of antibiotics has resulted in the emergence of drug-resistant populations of microorganisms. Clearly, one can see the need to develop new, more effective, antimicrobial agents that go beyond the explored 'chemical space'. In this regard, their unique modes of action (e.g., reactive oxygen species (ROS) generation, redox activation, ligand exchange, depletion of substrates involved in vital cellular processes) render metal complexes as promising drug candidates. Several Ru (II/III) complexes have been included in, or are currently undergoing, clinical trials as anticancer agents. Based on the in-depth knowledge of their chemical properties and biological behavior, the interest in developing new ruthenium compounds as antibiotic, antifungal, antiparasitic, or antiviral drugs has risen. This review will discuss the advantages and disadvantages of Ru (II/III) frameworks as antimicrobial agents. Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru (II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein.

摘要

抗生素的广泛使用导致了耐药微生物群体的出现。显然，可以看出有必要开发新的、更有效的抗菌剂，这些抗菌剂要超越已探索的“化学空间”。在这方面，它们独特的作用方式（例如，活性氧（ROS）生成、氧化还原激活、配体交换、消耗参与重要细胞过程的底物）使金属配合物成为有前景的药物候选物。几种钌（II/III）配合物已被纳入或正在进行作为抗癌剂的临床试验。基于对其化学性质和生物学行为的深入了解，开发新型钌化合物作为抗生素、抗真菌药、抗寄生虫药或抗病毒药的兴趣有所增加。本综述将讨论钌（II/III）骨架作为抗菌剂的优缺点。还讨论了它们的化学结构与作用机制、细胞定位和/或钌配合物在细菌和真核细胞中的代谢之间关系的一些方面。关于抗病毒活性，鉴于与新冠疫情相关的当前事件，本文还综述了用于对抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的钌（II/III）化合物（例如，BOLD-100）。

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