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对抗抗菌药物耐药性:抗菌研究中的创新药物

Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.

作者信息

Süssmuth Roderich D, Kulike-Koczula Marcel, Gao Peng, Kosol Simone

机构信息

Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, TC2, 10629, Berlin, Germany.

Medical School Berlin, Department Human Medicine, Rüdesheimer Strasse 50, 14195, Berlin, Germany.

出版信息

Angew Chem Int Ed Engl. 2025 Mar 3;64(10):e202414325. doi: 10.1002/anie.202414325. Epub 2025 Feb 10.


DOI:10.1002/anie.202414325
PMID:39611429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11878372/
Abstract

In the fight against bacterial infections, particularly those caused by multi-resistant pathogens known as "superbugs", the need for new antibacterials is undoubted in scientific communities and is by now also widely perceived by the general population. However, the antibacterial research landscape has changed considerably over the past years. With few exceptions, the majority of big pharma companies has left the field and thus, the decline in R&D on antibacterials severely impacts the drug pipeline. In recent years, antibacterial research has increasingly relied on smaller companies or academic research institutions, which mostly have only limited financial resources, to carry a drug discovery and development process from the beginning and through to the beginning of clinical phases. This review formulates the requirements for an antibacterial in regard of targeted pathogens, resistance mechanisms and drug discovery. Strategies are shown for the discovery of new antibacterial structures originating from natural sources, by chemical synthesis and more recently from artificial intelligence approaches. This is complemented by principles for the computer-aided design of antibacterials and the refinement of a lead structure. The second part of the article comprises a compilation of antibacterial molecules classified according to bacterial target structures, e.g. cell wall synthesis, protein synthesis, as well as more recently emerging target classes, e.g. fatty acid synthesis, proteases and membrane proteins. Aspects of the origin, the antibacterial spectrum, resistance and the current development status of the presented drug molecules are highlighted.

摘要

在对抗细菌感染,尤其是由被称为“超级细菌”的多重耐药病原体引起的感染方面,科学界对抗菌新药的需求是毋庸置疑的,而且目前也已被广大民众广泛认识到。然而,在过去几年中,抗菌药物研究格局发生了很大变化。除了少数例外,大多数大型制药公司已退出该领域,因此,抗菌药物研发的减少严重影响了药物研发进程。近年来,抗菌药物研究越来越依赖规模较小的公司或学术研究机构,这些机构大多资金有限,要从一开始就承担药物发现和开发过程,直至临床阶段初期。本综述阐述了针对目标病原体、耐药机制和药物发现的抗菌药物要求。展示了从天然来源发现新抗菌结构、通过化学合成以及最近通过人工智能方法的策略。计算机辅助设计抗菌药物和优化先导结构的原则对此起到了补充作用。文章的第二部分汇编了根据细菌靶标结构分类的抗菌分子,例如细胞壁合成、蛋白质合成,以及最近出现的靶标类别,例如脂肪酸合成、蛋白酶和膜蛋白。突出介绍了所展示药物分子的来源、抗菌谱、耐药性和当前开发状况等方面。

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