天然产品托尼尔具有复杂的抗菌机制,并针对多个点
Felix Deschner1, Dietrich Mostert2, Jan-Martin Daniel3
1Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123 Saarbrücken, Germany; Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany; Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany; German Centre for Infection Research (DZIF), partner sites: Bonn-Cologne, Hannover-Braunschweig, and Tübingen, 38124 Braunschweig, Germany.
Cell chemical biology
|April 9, 2025
概括
新的天然产品称为托尼尔,显示出广泛的抗菌活性. 它们向细菌细胞膜和蛋白质生物合成,提供了对抗耐药性感染和疟疾的有希望的战略.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 自然产品 化学 化学
背景情况:
- 抗菌素耐药性 (AMR) 构成了全球健康的重大威胁,需要开发新型治疗剂.
- 现有的抗生素对抗多药耐药 (MDR) 病原体变得无效.
- 自然产品为发现具有新型作用机制的新抗菌化合物提供了丰富的来源.
研究的目的:
- 阐明托尼尔的作用模式,一种具有被证明具有广谱活性的自然产品类.
- 调查类作为新型治疗药物对抗耐药细菌和疟疾的潜力.
- 为了表征特定的分子点和细胞作用的色素.
主要方法:
- 在体外测试以评估抗微生物活性对格拉姆阳性细菌和Plasmodium falciparum.
- 细胞和生物化学试验,以调查与细菌膜,细胞壁和蛋白质生物合成途径的托尼尔相互作用.
- 鼠感染模型,以评估体内疗效和安全性.
主要成果:
- хлоротонил通过破坏离子稳态和引起膜脱极化而表现出迅速开始的作用,而无需显著的细胞溶解.
- 确认了与细菌膜脂质的特定结合,导致不受控制的运输.
- 确定的二级标包括糖生物合成蛋白YbjG和甲氨基酶 (MetAP).
- 在小鼠感染模型中观察到有前途的活性和安全性.
结论:
- 托尼尔是一种新型的抗微生物药物,具有多目标作用机制.
- 它们干扰细胞膜完整性,离子运输和必需蛋白质生物合成的能力,为打击抗菌素耐药性提供了一个有希望的途径.
- 叶绿素的进一步开发可能会导致对细菌感染和疟疾的新疗法.
相关概念视频
01:27Combined Effects of Drugs: Synergism
3.6K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.6K
01:26Targets for Drug Action: Overview
5.9K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
5.9K
00:57Antibiotic Selection
52.0K
Overview
52.0K
01:23Antimicrobial Proteins
751
Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
751
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.5K